Noradrenaline Ratio Research Articles

Urinary Catecholamine and Metanephrine to Creatinine Ratios in Healthy Dogs at Home and in a Hospital Environment and in 2 Dogs with Pheochromocytoma

Measurement of high concentrations of urine catecholamines and metanephrines is useful in diagnosing pheochromocytoma in humans. Stress increases catecholamine excretion in urine. Stress of a hospital visit increases urinary catecholamine and metanephrine excretion in dogs. Fourteen clinically normal dogs, 2 dogs with pheochromocytoma. Voided urine samples were collected by the owners 7 days before (t-7), during the hospital visit immediately after diagnostic procedures (t0), as well as 1 (t1) and 7 days (t7) after the hospital visit. Urine catecholamine and metanephrine concentrations were measured using high-pressure liquid chromatography and expressed as ratios to urine creatinine concentration. In client-owned dogs epinephrine and norepinephrine ratios at t0 were significantly higher compared with ratios at t7. Metanephrine and normetanephrine ratios at t-7, t0, and t1 did not differ significantly from each other; however, at t7 they were significantly lower compared to values at t-7. In staff-owned dogs no significant differences were detected among the different collecting time points for any variable. Metanephrine and normetanephrine ratios were significantly higher in client-owned dogs compared to staff-owned dogs at t-7, t0, and t1 but not at t7. Stress associated with a hospital visit and with the sampling procedure causes increases in urine catecholamine and metanephrine excretion. Urine collection for the diagnosis of pheochromocytoma probably should take place at home after adaptation to the sampling procedure.

Effects of Methylphenidate on the Hyperemotional Behavior in Olfactory Bulbectomized Mice by Using the Hole-Board Test

The most consistent behavioral changes caused by olfactory bulbectomy are hyperemotional responses such as hyperactivity in a novel environment. However, the changes in the emotional behavior of mice after undergoing olfactory bulbectomy have not yet been described in detail. The effects of methylphenidate on the hyperemotional behavior of olfactory bulbectomized (OBX) mice were examined by using the hole-board test. Mice (4-week-old) were subjected to olfactory bulbectomy, and the behavioral test was performed 2 weeks after surgery. OBX mice showed a significant increase in the number of head-dips as compared to the sham-operated mice. This increase was significantly decreased after treatment with methylphenidate (10 µg/kg, s.c.). The norepinephrine (NE) turnover ratio in the frontal cortex in OBX mice was significantly less than that in the sham-operated mice. However, the decreased NE ratio in OBX mice normalized after treatment with methylphenidate. Our results suggest that the increased head-dipping behavior in OBX mice might reflect an impulsive-like behavior. In addition, we proposed that the improvement in the noradrenergic abnormalities in the frontal cortex due to methylphenidate treatment may play a key role in the improvement of impulsive-like behaviors observed in OBX mice.

Characterization of monoaminergic systems in brain regions of prematurely ageing mice

We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration (“slow mice”) being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

Sympathoadrenal imbalance before neurocardiogenic syncope

Neurocardiogenic syncope is the most common cause of acute loss of consciousness in adults. The present study attempted to identify neuroendocrine and hemodynamic changes before syncope that could therefore play a pathophysiologic role. Twenty-five patients referred for chronic orthostatic intolerance had plasma catecholamines measured serially; 21 patients during tilt-table testing (evoking syncope in 13) and 4 others with spontaneous syncope while supine. Forearm blood flow was measured by impedance plethysmography. All 12 patients with blood sampled before tilt-induced syncope had progressive, marked increases in plasma epinephrine levels (mean 11 times baseline, p <0.0001) before syncope. Simultaneously obtained norepinephrine levels increased to a much smaller extent than did epinephrine levels (“sympathoadrenal imbalance”). In the same patients, forearm vascular resistance decreased by 21% before syncope. Proportionate changes in forearm vascular resistance before syncope correlated negatively with those in the epinephrine:norepinephrine ratio (r = −0.75, p = 0.005). Patients without syncope had forearm vasoconstriction and no sympathoadrenal imbalance during tilt. Patients with syncope while supine also had sympathoadrenal imbalance before loss of consciousness. Sympathoadrenal imbalance precedes tilt-evoked and spontaneous neurocardiogenic syncope and correlates with concurrent skeletal muscle vasodilation. Sympathoadrenal imbalance may contribute to hemodynamic derangements precipitating neurocardiogenic syncope.

Active and passive membrane properties of rat sympathetic preganglionic neurones innervating the adrenal medulla.

The intravascular release of adrenal catecholamines is a fundamental homeostatic process mediated via thoracolumbar spinal sympathetic preganglionic neurones (AD-SPN). To understand mechanisms regulating their excitability, whole-cell patch-clamp recordings were obtained from 54 retrogradely labelled neonatal rat AD-SPN. Passive membrane properties included a mean resting membrane potential, input resistance and time constant of -62 +/- 6 mV, 410 +/- 241 MOmega and 104 +/- 53 ms, respectively. AD-SPN were homogeneous with respect to their active membrane properties. These active conductances included transient outward rectification, observed as a delayed return to rest at the offset of the membrane response to hyperpolarising current pulses, with two components: a fast 4-AP-sensitive component (A-type conductance), contributing to the after-hyperpolarisation (AHP) and spike repolarisation; a slower prolonged Ba(2+)-sensitive component (D-like conductance). All AD-SPN expressed a Ba(2+)-sensitive instantaneous inwardly rectifying conductance activated at membrane potentials more negative than around -80 mV. A potassium-mediated, voltage-dependent sustained outward rectification activated at membrane potentials between -35 and -15 mV featured an atypical pharmacology with a component blocked by quinine, reduced by low extracellular pH and arachidonic acid, but lacking sensitivity to Ba(2+), TEA and intracellular Cs(+). This quinine-sensitive outward rectification contributes to spike repolarisation. Following block of potassium conductances by Cs(+) loading, AD-SPN revealed the capability for autorhythmicity and burst firing, mediated by a T-type Ca(2+) conductance. These data suggest the output capability is dynamic and diverse, and that the range of intrinsic membrane conductances expressed endow AD-SPN with the ability to generate differential and complex patterns of activity. The diversity of intrinsic membrane properties expressed by AD-SPN may be key determinants of neurotransmitter release from SPN innervating the adrenal medulla. However, factors other than active membrane conductances of AD-SPN must ultimately regulate the differential ratio of noradrenaline (NA) versus adrenaline (A) release secreted in response to various physiological and environmental demands.

Long-term prenatal hypoxia alters maturation of adrenal medulla in rat.

Catecholamine release from the adrenal medulla glands plays a vital role in postnatal adaptation. A number of pathologic situations are characterized by oxygen deficiency. The objective of the present study was to determine the influence of long-term prenatal hypoxia on maturation of the adrenal medulla. Pregnant rats were subjected to hypoxia (10% O2) from the fifth to the 20th d of gestation. The offspring were examined on the 19th d of gestation (E19), the day of birth (P0), and at postnatal (P) day of life P3, P7, P14, P21, and P68. The catecholamine content and activity of tyrosine hydroxylase (TH) in vivo were assayed by HPLC with electrochemical detection. Cellular expression of TH and phenylethanolamine N-methyl transferase was evaluated by protein immunohistochemistry and in situ hybridization of the corresponding mRNA species. Exposure to prenatal hypoxia reduced the epinephrine content of the adrenal medulla on E19, P0, P3, and P7 while increasing the norepinephrine content on E19, P0, and P14. Furthermore, the peak epinephrine to norepinephrine ratio appearing between P7 and P10 in the normoxic offspring was absent in the hypoxic offspring. The in vivo TH activity was increased on P3 and P14 and decreased on P68. The percentage of chromaffin cells in the medulla expressing TH and phenylethanolamine N-methyl transferase was lowered on E19, P0, and P7. TH and phenylethanolamine N-methyl transferase mRNA levels were reduced on P7. Clearly prenatal hypoxia results in major changes in adrenal catecholamine stores and synthesis during the perinatal period, which persist into adulthood. The capacity to cope with postnatal stress might be disturbed as a consequence of prenatal hypoxia.

Catecholamines in human saliva

Catecholamines are readily detectable in human saliva but their origin is unclear. Norepinephrine (NE) was stable in saliva stored at 4 degrees for 2 hours but 11 +/− 3% degraded after storage at 25 degrees for 1 hour. We intravenously infused 3H-NE into humans and measured levels of 3H-NE and its metabolites in both saliva and forearm venous plasma (a site whose plasma NE levels reflect both local uptake and release of NE). 3H-NE levels in saliva continued to rise for 1 hour even though forearm plasma levels had plateaued by 5 min. By 65 min into the infusion the ratio of 3H-NE:non-radioactive NE was similar in saliva and forearm venous plasma. The ratio of NE:epinephrine (E) was similar in saliva and forearm venous plasma at all time points. Chewing induced salivation, and at least tripled the amount of NE, E and 3H-NE released into saliva per minute, but decreased their concentration in saliva by as much as one half. Saliva NE level was unaltered after 15 min of standing but was increased by 31% after 1 hour of upright posture. Our data imply that the NE present in human saliva comes from both the bloodstream and from salivary sympathetic nerves. The finding that diffusion of blood NE into saliva takes roughly 1 hour to complete suggests that NE in saliva is a poor index of acute changes in sympathetic activity.

Correlation of increased grooming behavior and motor activity with alterations in nigrostriatal and mesolimbic catecholamines after alpha-melanotropin and neuropeptide glutamine-isoleucine injection in the rat ventral tegmental area.

1. We wished to further study the behavioral effects of alpha-melanotropin (alpha-MSH), melanin-concentrating hormone (MCH), and neuropeptide glutamine-isoleucine (NEI). 2. To this effect we administered alpha-MSH, MCH, and NEI in the ventral tegmental area of the rat, a structure where these neuropeptides are highly concentrated. To further elucidate the biochemical mechanisms of the behavioral effect of these neuropeptides, we determined the degree of grooming behavior and the levels of catecholamines. after neuropeptide administration. 3. We preselected those animals responding to the central injection of alpha-MSH with excessive grooming behavior. We administered the neuropeptides at the dose of 1 microg/0.5 microL, in each side of the ventral tegmental area, bilaterally. We studied grooming behavior, locomotor activity, and total behavior scores, 30 and 65 min after administration of the peptides. 4. Three groups of animals were decapitated immediately after the injection of the neuropeptides, and 30 or 65 min after injection. We measured dopamine (DA), noradrenaline (NA), and the dopac/dopamine ratio (DOPAC/DA) to determine steady state levels of catecholamines and an indirect measure of DA release and metabolism, respectively. 5. Injections of alpha-MSH produced significant elevations in grooming behavior, locomotor activity, and total behavior scores, both 30 and 65 min after peptide administration. This was correlated with significant decreases in DA content, increases in DOPAC content, and increases in the DOPAC/DA ratio. In the caudate putamen, changes in catecholamines occurred both at 30 and 65 min after injection. In the nucleus accumbens, changes were present at 65 min after injection. Conversely, there were no alterations in NA content, either in the caudate putamen or in the nucleus accumbens, at any time after the injection. 6. Injections of NEI resulted in significant elevations in grooming behavior, locomotor activity, and total behavior scores, both 30 and 65 min after peptide administration. This was correlated with increased DOPAC/DA ratio in the nucleus caudatus but not in the nucleus accumbens. Conversely, NEI produced increased NA concentrations in the nucleus accumbens, but not in the nucleus caudatus. 7. Injections of MCH did not produce significant changes in behavior or significant changes in nucleus caudatus or nucleus accumbens catecholamines. 8. Our results indicate (a) There is a correlation with alterations in behavior as induced for the neuropeptides injected here, and changes in extrapyramidal catecholamines. (b) There is a correlation between alterations in behavior and increases in DOPAC/DA ratio in the nucleus caudatus. (c) There is a correlation between alterations in behavior and alterations in catecholamines in the nucleus accumbens. In the nucleus accumbens, DOPAC/DA ratio is changed after alpha-MSH, and NA ratio is changed after NEI injection. (d) Absence of alterations in extrapyramidal catecholamines, and in particular in catecholamines in the nucleus accumbens, correlates with absence of behavioral alterations after neuropeptide administration to the ventral tegmental area. 9. In conclusion, the behavioral effect of exogenous administration of neuropeptides in the ventral tegmental area is peptide-specific, and is probably associated with alterations in catecholamine metabolism and release in the nucleus caudatus and the nucleus accumbens. Both alpha-MSH and NEI seem to stimulate the nigrostriatal DA system. While alpha-MSH appears to stimulate the mesolimbic DA system as well, NEI may exert its actions not through the DA, but through the NA mesolimbic system. The precise contribution of DA and NA, and the relative role of the nucleus caudatus and nucleus accumbens in these behaviors remain to be elucidated.

Diabetes attenuates the response of the lumbospinal noradrenergic system to idazoxan

Allodynia is a common feature of painful diabetic neuropathy. This phenomenon appears to be under endogenous noradrenergic control and can be ameliorated effectively by α 2-adrenoceptor agonists. Accordingly, diabetic lumbospinal noradrenergic dynamics was evaluated using high performance liquid chromatography with electrochemical detector (HPLC-ECD), in vitro ligand binding and RT–PCR-based techniques. Streptozotocin (STZ)-treated and Goto–Kakizaki (GK) diabetic rats were included, respectively, as models for type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus. The data from these studies revealed that lumbospinal norepinephrine (NE) release, as indicated by the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NE ratio, was decreased as a function of diabetes. Similarly, the binding density of [ 3H] p-aminoclonidine and the level of expression of mRNA transcripts encoding for the α 2A-adrenoceptor subtype and noradrenergic transporter were also reduced in this disease state. Analogous findings were obtained in non-diabetic Wistar rats rendered hypercortisolemic by the subcutaneous implantation of slow releasing pellets containing a supraphysiological dose of glucocorticoid (GC). Tactile allodynia was consistently observed in STZ- and GC-treated animals. The responsiveness of α 2-adrenoceptors to idazoxan (α 2-adrenoceptor antagonist) indicated a dose-dependent enhancement of noradrenergic transmission in lumbar segments of normal spinal cord. In stark contrast, this neurochemical action of idazoxan was attenuated in diabetic and hypercortisolemic animals. The institution of insulin therapy ameliorated diabetes-related abnormalities in lumbospinal noradrenergic dynamics. Overall, the current finding suggests that diabetic and hypercortisolemic allodynic symptoms may stem from, at least in part, down-regulation of α 2-adrenoceptors in these disease states.

Insulin-like growth factor 1-induced alterations in lumbospinal monoamine dynamics.

A wealth of evidence indicates that insulin-like growth factor (IGF-1) is involved in neurotransmitter release, synaptic plasticity, morphogenesis and regulation of gene expression. RT-PCR and immunocytochemical-based techniques revealed that IGF-1 and its receptor are highly expressed by different neuronal elements of the spinal cord lumbar enlargement. Accordingly, the present study intended to examine lumbospinal monoamine dynamics in the context of the neurotrophic factor IGF-1. Spinal release of norepinephrine (NE) represented by 3-methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was enhanced by IGF-1. This action of IGF-1 was associated with a similar increase in both tyrosine hydroxylase (TH) immunoreactivity and the level of its mRNA. In contrast, neuronal contents of serotonin and its metabolite 5-hydroxyindoleacetic acid in IGF-1-treated animals remained at control level. Genistein, a tyrosine kinase inhibitor, which by itself had no effect on NE metabolism, abolished the induction effect of IGF-1 on TH and MHPG/NE ratio. Our results suggest that IGF-1 augments the lumbospinal noradrenergic system by an intracellular mechanism involving a receptor-linked tyrosine kinase. The physiological consequences of the IGF-1 actions are discussed in terms of neuroprotection and nociception.

Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states

Disorders of pain sensation including spontaneous pain, allodynia and hyperalgesia are commonly seen in neuropathic diabetic patients. A wealth of evidence indicates that spinal monoamine systems are implicated in pain modulation but whether abnormalities in these systems underlay such disorders is unclear. The present study was therefore initiated to investigate spinal noradrenergic dynamics during diabetes. Spinal release of norepinephrine (NE) represented by 3-methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was markedly suppressed in 30-day streptozotocin (STZ)-treated diabetic male and female rats. The density of [ 3 H ] p-aminoclonidine binding sites and the level of expression of mRNA encoding for α 2A-adrenoceptor subtype were also reduced as a function of diabetes. In contrast, an increase in the density of [ 3 H ] prazosin binding to spinal synaptosomal membranes was evident in these animals. Clonidine-induced elevation in nociceptive threshold was attenuated in diabetics. Control animals subjected to chronic treatment with a supraphysiological dose of glucocorticoid (GC) exhibited a neurochemical pattern which is similar in many respects to that produced by the diabetic state. Both insulin and the GC receptor blocker, RU 486, restored most of the neurochemical and behavioural abnormalities of diabetes. Overall, the present study supports the concept that a diabetes-related deficit in spinal noradrenergic dynamics may be a reflection of an overactivity of the hypothalamic–pituitary–adrenal axis.

Dysregulation of cardiovascular and neuroendocrine responses to stress in premenstrual dysphoric disorder

Twelve women with prospectively confirmed premenstrual dysphoric disorder (PMDD or PDD) were compared with 12 healthy control subjects for cardiovascular and neuroendocrine responses to speech and mental arithmetic (Paced Auditory Serial Addition Task) stressors during both the follicular and luteal phases of the menstrual cycle. Structured clinical interview was used to assess psychiatric and abuse histories, and standardized questionnaires were administered to assess current life stress. Results revealed that PMDD women had significantly lower stroke volume, cardiac output and cortisol levels but significantly elevated norepinephrine and total peripheral resistance at rest and also during mental stressors compared with control subjects. These effects were evident in both cycle phases. Significantly more women with PMDD had histories of sexual abuse, and they also reported greater current life stress than control subjects. Consistent with a history of trauma, the PMDD women exhibited significantly greater ratios of norepinephrine to cortisol at rest and during stress. These results are interpreted as reflecting dysregulation of the stress response and may be related to histories of severe and/or chronic exposure to stress for a subgroup of PMDD women.

Sex-dependent differences in the concentrations of the principal neurotransmitters, noradrenaline and acetylcholine, in the three major salivary glands of mice

The concentrations of principal neurotransmitters in the submandibular, parotid and sublingual glands were compared between two pairs of age-matched male and female ddY mice, one pair consisting of 4-week-old and the other 8-week-old animals. Sex-dependent differences in both noradrenaline and acetylcholine concentrations were observed only in the submandibular gland, although each neurotransmitter showed distinct features. The acetylcholine concentration in the submandibular gland was higher in the female at both ages, whereas the noradrenaline concentration was higher in the female at the age of 4 weeks but became higher in the male by the age of 8 weeks. On the other hand, the total amounts of noradrenaline and acetylcholine per submandibular gland were already greater in the male at 4 weeks, and the male parotid and sublingual glands also had a greater noradrenaline content by 4 weeks and 8 weeks, respectively. Each type of gland had similar growth rates over the 4-week period, and the male submandibular and parotid glands were heavier than the female. In addition, each type of gland had its characteristic ratio of noradrenaline to acetylcholine concentration, which did not differ between the sexes and remained in similar basic patterns during the period examined, except for the submandibular gland of 8-week-old male mice, which developed greater amounts of the sympathetic neurotransmitter noradrenaline.

A Preliminary Study of the Effects of Venlafaxine on 24‐Hour Urinary Catecholamine Excretion Profile

Objective: To investigate the effects of venlafaxine on the 24‐hour urinary catecholamine excretion profile in patients treated with this drug for depression.Method: Patients to be treated with venlafaxine for the management of a depressive illness were requested to provide a 24‐hour urine sample immediately before the commencement of therapy. The urinary concentrations of adrenaline and noradrenaline were determined, and the 24‐hour urinary catecholamine excretion profile was calculated. This procedure was repeated after treatment with venlafaxine for 14 days.Results: Eight patients were enrolled in the study, but three patients did not complete the protocol because of adverse drug reactions. The effects of venlafaxine treatment on the profile of urinary catecholamine excretion were assessable in five patients. The mean 24‐hour excretion of noradrenaline appeared to be decreased after venlafaxine treatment, but this decrease failed to attain statistical significance. The 24‐hour urinary excretion of adrenaline was unchanged after venlafaxine, but the ratio of noradrenaline:adrenaline urinary excretion decreased significantly after treatment.Conclusions: This small prospective study demonstrates an altered profile of urinary catecholamine excretion in patients treated with venlafaxine for depression for two weeks. Further research is needed to determine whether there is a correlation between the effects of venlafaxine on urinary noradrenaline excretion and the therapeutic and/or adverse effects of this antidepressant.Aust J Hosp Pharm 1997; 27: 232–3.

Noradrenergic neurons release both noradrenaline and neuropeptide Y from a single pool: the large dense cored vesicles.

In peripheral adrenergic nerve endings, noradrenaline is stored in two different types of vesicles, the large and the small dense cored vesicles. A systematic study was undertaken to examine the release of noradrenaline and neuropeptide Y from dog spleen and rat vas deferens under various conditions of stimulation, particularly those which previously have demonstrated a differential regulation of exocytosis of the different types of storage vesicles. Here we present evidence that noradrenaline is released by exocytosis exclusively from the large dense cored vesicles, in which it is stored together with neuropeptide Y. Upon a single stimulation (at frequencies varying from 2-20 Hz), the release of noradrenaline and neuropeptide Y from the dog splenic nerve increased with the frequency of stimulation, but the ratio of noradrenaline to neuropeptide Y remained constant. After repeated stimulation of the splenic nerve, both substances' overflow decreased gradually and in parallel to values of 12.5% and 11.1% of the first stimulation for noradrenaline and neuropeptide Y, respectively. Similarly, repeated stimulation of the rat vas deferens (of which only 2-10% is large dense cored vesicles, whereas in the dog splenic nerve the large dense cored vesicles make up 30-40% of the total vesicle population) with 120 mM K+, in the presence of phentolamine, caused a gradual and parallel decline in the release of noradrenaline and neuropeptide Y (31.6% and 34.0%, respectively). Moreover, omega-conotoxin (10(-8) M to 10(-5) M) had a similar inhibitory effect on the release of both substances, alpha-latrotoxin (10(-9) M) evoked a parallel release of both noradrenaline and neuropeptide Y. The results indicate that noradrenaline in peripheral noradrenergic nerves is released exclusively from large dense cored vesicles by an exocytotic mechanism.

Responses to novelty stress in female F344 rats: Effects of age and d-fenfluramine treatment

To elucidate some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with age in female rats, we administered the serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine( d-FEN; 0.0 or 0.6 mg/kg/day, PO) for 30–38 days to young (4 month) and old (21 month) F-344 female rats. Animals were placed into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited significantly ( p < 0.05) less exploratory behavior and a smaller CORT response to OF than young animals. rf-FEN treatment had no effect on plasma ACTH and CORT levels or exploratory behavior. The old HC rats had significantly ( p < 0.05) higher plasma levels of prolactin (PRL) than the young HC rats. A stress induced increase in PRL secretion was observed in the old rats only, which was attenuated by d-FEN treatment. In the OF groups, both the young and old rats showed elevated medial frontal cortex (MFC) dopamine turnover ( DOPAC DA ratio), but only the young rats exhibited an elevation in norepinephrine (NE) turnover ( MHPG NE ratio). d-FEN treatment blocked the stress-induced increase in NE turnover in the young rats and the increase in DA turnover in the old rats. These data suggest that 5-HT activity could be involved in the age-related changes in the MFC catecholamine and PRL responses to stress in female rats.

PACAP stimulates catecholamine release from adrenal medulla: a novel noncholinergic secretagogue.

The secretory response of the adrenal medulla to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel polypeptide with 68% structural homology to vasoactive intestinal polypeptide (VIP), was investigated in anesthetized rats by in vivo microdialysis. The injection of PACAP (1.5 nmol) caused a greater amount of increase in catecholamine concentration than carbachol (30 nmol) or VIP (30 nmol) in the dialysate for a period of 60 min. The ratios of norepinephrine to epinephrine in the dialysate after stimulation with these compounds showed no change from resting conditions. The simultaneous application of both nicotinic and muscarinic antagonists (10 mM mecamylamine and 1 mM atropine) eliminated the increase in catecholamine secretion induced by carbachol. In contrast, PACAP-induced catecholamine secretion was not inhibited by these cholinergic antagonists. These data led to the following conclusions: 1) PACAP was more potent than either carbachol or VIP in enhancing the secretion of catecholamine from the adrenal medulla, and 2) PACAP-induced catecholamine secretion was due to the direct action of PACAP on the adrenal medulla rather than an indirect action mediated by acetylcholine release. These results strongly suggest that PACAP is a noncholinergic secretagogue of the adrenal medulla in rats.

Effect of arterially infused catecholamines and insulin on plasma glucose and free fatty acids in carp.

Common carp (Cyprinus carpio L.), kept at 20 degrees C, were fitted with an indwelling PE-50 cannula in the dorsal aorta. Hormones dissolved in Ringer saline were arterially infused at a rate of 1 microgram.kg-1.min-1 for epinephrine (Epi), 2 micrograms.kg-1.min-1 for norepinephrine (NE), and 1.33 micrograms.kg-1.min-1 for insulin. INfusion of bovine insulin in carp resulted in a long lasting (24 h) decrease of plasma free fatty acids (FFA; -0.41 +/- 0.06 mM) and glucose levels (-3.14 +/- 0.25 mM) compared with preinfusion levels at t = 0. Both Epi and NE induced a marked hyperglycemia although Epi was more potent (+8.2 +/- 0.9 and +6.9 +/- 0.8 mM, respectively). Plasma FFA levels increased by 0.25 +/- 0.03 mM compared with preinfusion levels on Epi infusion. In contrast, during NE infusion, plasma FFA levels decreased significantly by -0.21 +/- 0.03 mM. Plasma insulin titers did not significantly change during infusion of NE or Epi. It is concluded that the ratio of NE to Epi is the major factor that determines the effect of catecholamines on plasma FFA levels in carp. These results may explain species-dependent different effects of hypoxia on FFA metabolism in fish.

Microgravity decreases tyrosine hydroxylase expression in rat adrenals

During spaceflight, alterations in blood and urinary catecholamine (CA) levels have been observed, yet the cellular/molecular mechanisms leading to these changes are not known. We used molecular, immunological, and biochemical approaches to analyze in situ the expression of catecholamine enzymes in adrenal medullary chromaffin cells of rats flown for 6 days on board Space Shuttle mission STS-54. Exposure to microgravity (10(-6) g) resulted in a 35% inhibition of both the expression and the specific activity of tyrosine hydroxylase (TH), the rate-limiting step in the cascade of CA synthesis. By contrast, the expression, specific activity, and immunoreactivity of other catecholamine-synthesizing enzymes, e.g., phenylethanolamine-N-methyl-transferase (PNMT), were not altered. The total tissue CA contents were reduced, concomitant with a decrease in the epinephrine:norepinephrine ratio. These results are in line with reports of other gravity-sensitive cellular effects and suggest that the inhibition of TH expression might be due to a direct effect of microgravity on PKC-dependent signal transduction pathways in chromaffin cells.

HUMORAL DETERMINANTS OF Na+ EXCRETION AFTER INTRAVENOUS NaCl LOADING IN NORMAL VOLUNTEERS

1. Twelve healthy volunteers maintained on a 100 mmol/day Na+ diet, were given an intravenous infusion of 2L saline (0.9%) between 10.00 h on 2 study days at least 1 week apart. Urine collections (90 min) were made from 08.30 to 16.00 h. Either carbidopa 100 mg or indomethacin 50 mg was given orally at 07.45 h on one study day and placebo was given on the other (in random order). 2. On the placebo day, saline infusion caused significant decreases in plasma albumin concentration, plasma renin activity (PRA), plasma aldosterone concentration and urinary aldosterone excretion, with 2 to 3-fold increases in plasma atrial natriuretic peptide (ANP) concentration and urinary dopamine: noradrenaline ratio (DA:NA), whereas mean urinary kallikrein and prostaglandin E2 (PGE2) excretion rates were unchanged. Carbidopa decreased urinary DA:NA and indomethacin decreased urinary PGE2 excretion, compared with the placebo day. Excretion of sodium (Na+) decreased below baseline in two out of six carbidopa-treated subjects and in three out of six indomethacin-treated subjects, but showed little or no change in the remainder. 3. These preliminary observations suggest that some subjects in the early phase of natriuresis after an intravenous Na+ load can be identified as having prostaglandin-dependent or dopamine-dependent mechanisms for Na+ excretion.