High Concentrations Of Catecholamines Research Articles

Serum cardiac troponin T after repeated endurance exercise events.

Recently Dr. Rowe made a hypothesis according to which small areas of myocardial necrosis can be caused by microvascular spasm, related to high catecholamine concentrations and other mechanisms, following extraordinary unremitting endurance exercises or due to the cumulative effect of several endurance events. It was this last suggestion which prompted us to investigate 25 top cyclists, taking part in the 77th Giro d'Italia. Blood samples were obtained the day before the start of the competition and once a week thereafter until the end. We measured myoglobin, lactic dehydrogenase, total creatine kinase, creatine kinase isoenzyme MB and serum cardiac troponin T (Tn-T), a highly sensitive and specific method for the detection of myocardial injury. While at measuring time points which followed we found a significant increase in the serum indicators of muscle damage, compared with their values at the beginning of the race, creatine kinase isoenzyme MB did not rise significantly and cardiac Tn-T was found in the serum of only 5 athletes, repeatedly in some cases, but always below the cut off values considered as indicating myocardial ischemia. On the basis of the behaviour of creatine kinase isoenzyme MB and, above all, of cardiac Tn-T, we can conclude that heavy endurance exercises, repeated daily for 22 days, as was the case in our study, do not seem able to produce, in top athletes, permanent heart damage by means of acute myocardial injury.

Catecholamines and Indoleamines in the Central Nervous System of a Urodele Amphibian: A Microdissection Study with Emphasis on the Distribution of Epinephrine (Part 2 of 2)

Individual brain nuclei and regions of the central nervous system of adult male roughskin newts (Taricha granulosa) were microdissected and the concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, and serotonin were determined using high performance liquid chromatography (HPLC) with electrochemical detection. The pattern of distribution of these catecholamines and indoleamines revealed many similarities between this urodele and other vertebrates. The highest concentrations of biogenic amines were observed in brainstem, hypothalamic, and basal forebrain structures; the lowest concentrations were observed in the internal granule layer of the olfactory bulb and pallial structures of the telencephalon. High concentrations of catecholamines and indoleamines were found in hypothalamic periventricular regions that are known to include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies. The rostral diencephalon, which included the preoptic recess organ, had high concentrations of the primary catecholamines, norepinephrine and dopamine, and extremely high concentrations of the secondary catecholamine epinephrine. The dorsomedial infundibular hypothalamic region, which included the paraventricular organ, had high concentrations of dopamine and serotonin. The lateral infundibular hypothalamic region, which included the nucleus infundibularis dorsalis, had high concentrations of each of the biogenic amines. The results revealed unique patterns of distribution for each of the catecholamines and indoleamines studied, and provided evidence that regions of the hypothalamus that include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies are focal regions for the metabolism of multiple biogenic amines.

Catecholamines and indoleamines in the central nervous system of a urodele amphibian: a microdissection study with emphasis on the distribution of epinephrine.

Individual brain nuclei and regions of the central nervous system of adult male roughskin newts (Taricha granulosa) were microdissected, and the concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, and serotonin were determined using high performance liquid chromatography (HPLC) with electrochemical detection. The pattern of distribution of these catecholamines and indoleamines revealed many similarities between this urodele and other vertebrates. The highest concentrations of biogenic amines were observed in brainstem, hypothalamic, and basal forebrain structures; the lowest concentrations were observed in the internal granule layer of the olfactory bulb and pallial structures of the telencephalon. High concentrations of catecholamines and indoleamines were found in hypothalamic periventricular regions that are known to include cerebrospinal fluidcontacting, monoamine-containing neuronal cell bodies. The rostral diencephalon, which included the preoptic recess organ, had high concentrations of the primary catecholamines, norepinephrine and dopamine, and extremely high concentrations of the secondary catecholamine epinephrine. The dorsomedial infundibular hypothalamic region, which included the paraventricular organ, had high concentrations of dopamine and serotonin. The lateral infundibular hypothalamic region, which included the nucleus infundibularis dorsalis, had high concentrations of each of the biogenic amines. The results revealed unique patterns of distribution for each of the catecholamines and indoleamines studied, and provided evidence that regions of the hypothalamus that include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies are focal regions for the metabolism of multiple biogenic amines.

Prolonged infusion of epinephrine down-regulates expression of the fatty acid synthase gene in adipocytes

Fatty acid synthase is a key enzyme in thede novo synthesis of fatty acids. Expression of fatty acid synthase mRNA in adipocytes is inhibited by beta adrenergic agonists. We wondered if prolonged exposure to high concentrations of catecholamines might inhibit expression of the fatty acid synthase gene in fat cells. In this study we investigated the effects of adrenergic stimulation on the regulation of fatty acid synthase in fat cells. Rats were infused continuously with epinephrine (60 μg/kg/hr) or vehicle for 48 h and fat pads were isolated. The infusion of epinephrine down-regulated expression of the fatty acid synthase mRNA as well as decreasing enzyme activity. Both epinephrine and isoproterenol inhibited fatty acid synthase mRNA expression when adipocytes were activatedin vitro. These effects were blocked by the β adrenergic antagonist propranolol. In contrast, incubation with the adenosine receptor agonist phenylisopropyl-adenosine which decreases cAMP accumulation in fat cells, caused an increase in accumulation of fatty acid synthase mRNA. These results indicate that prolonged exposure to catecholamines, acting via β adrenergic receptors, inhibit expression of the fatty acid synthase gene possibly by increasing intracellular concentrations of cAMP.

Parasympathetic muscarinic stimulation limits noradrenaline induced myocardial creatine kinase release: a study in the isolated perfused working rat heart.

It has long been known that high concentrations of catecholamines may induce myocardial damage, and aggravate ischaemic injury. It has also been shown that beta-blockade may protect the myocardium from ischaemic damage. Stimulation of muscarinic receptors modulates beta-adrenergic receptor affinity for isoproterenol and attenuates isoproterenol induced adenylyl cyclase activation. Effects of muscarinic receptor stimulation were therefore investigated in isolated anterogradely perfused rat hearts under different experimental conditions. One group of hearts was perfused with noradrenaline, 10(-6) mol l-1 for 45 min, and another group was perfused with different carbachol concentrations (3 x 10(-7)-10(-5) mol l-1) with or without noradrenaline 10(-6) mol l-1, for 45 min. Release of creatine kinase to the perfusion buffer was taken as a sign of cell damage. Heart rate, left ventricular maxdP/dt and left ventricular pressure were measured throughout the perfusion time by insertion of a 20 gauge cannula through the left ventricular wall near the base. Carbachol (3 x 10(-7) mol l-1) alone induced a decrease of heart rate by 25% and maxdP/dt by 13%. Noradrenaline produced a 20% increase in heart rate, whereas the combination of noradrenaline plus carbachol induced a minor decrease in heart rate. Muscarinic receptor stimulation alone decreased myocardial contractility. However, when combined with noradrenaline no decrease in contractility was seen. Also, the release of creatine kinase to the perfusion buffer containing the combination of carbachol plus noradrenaline was reduced. Thus, muscarinic receptor stimulation protected the myocardium from catecholamine induced damage at concentrations where no change in contractility was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of acute exercise on levels of erythrocyte 2,3-bisphosphoglycerate: a brief review.

The effects of acute and chronic exercise on factors related to oxygen transport have been studied extensively. This process has led investigators to quantify the relationship between variables such as exercise mode and intensity, and red cell 2,3-bisphosphoglycerate (2,3-BPG) concentration. Anaerobic forms of exercise associated with a large blood lactate appearance and greatly elevated catecholamines initially decrease 2,3-BPG after exercise due to inhibited glycolysis, but there appears to be a delayed increase if sampling is continued into recovery. Aerobic forms of exercise have shown both increases and decreases. Therefore, whether 2,3-BPG is increased or decreased during and after exercise appears to be related to the exercise and blood sampling protocols employed. Further research involving resistance exercise protocols eliciting very high blood lactate and catecholamine concentrations may be beneficial in establishing a relationship between sympathetic stress response and the serial sampling of 2,3-BPG in the post-exercise recovery period. Also, in vitro analysis of the effects of the catecholamines, oxygen tension, lactate and adenosine may be helpful in understanding the dose-response relationship between these variables and 2,3-BPG concentration.

The role of cAMP in regulating the ?-adrenergic response of rainbow trout (Oncorhynchus mykiss) red blood cells

The β-adrenergic response of teleost red blood cells (RBCs) enables the fish to maintain or even enhance the oxygen affinity of haemoglobin during various stress situations. The role of CAMP in the pronounced β-adrenergic response of hypoxic rainbow trout RBCs was studied. Rainbow trout RBCs were incubated with three different β-agonists (noradrenaline, adrenaline and isoproterenol, 10(-9) - 10(-4) M) at two oxygen tensions (PO 2, 155 and 8 mmHg), and thereafter cAMP accumulation and cellular water content were measured.The cAMP concentration of non-stimulated trout RBCs was ca. 1200 nmol/kg dw. Of the three β-agonists used, isoproterenol was the most effective in formation of cAMP, followed by noradrenaline and adrenaline. Oxygen tension affected the accumulation of cAMP in two ways. At physiological catecholamine levels (1-100 nM) there was either no difference between normoxic and hypoxic cells or a slight increase in the normoxic ones. At high catecholamine concentrations the accumulation of cAMP was greater in the hypoxic than in the normoxic cells. Oxygen tension also affected the magnitude of cell swelling but had no effect on the catecholamine concentrations causing half-maximal swelling (EC50-values). The results indicate that, at physiological catecholamine levels, the β-adrenergic response of rainbow trout RBCs is mainly regulated on the level of the Na(+)/H(+) exchange.

Coexistence of beta 1-, beta 2-, and beta 3-adrenoceptors in dog fat cells and their differential activation by catecholamines

The existence of a beta 3-adrenoceptor (in addition to classical beta 1- and beta 2-), its involvement in the control of lipolysis and its recruitment by catecholamines were investigated in dog adipose tissue. Isoproterenol, norepinephrine, and the beta 2-selective agonist procaterol fully activated lipolysis in adipocytes (order of potency: isoproterenol > norepinephrine = procaterol). beta 3-Adrenergic agonists stimulated lipolysis with the order of potency: BRL 37344 > CGP 12177 > SR 58611A. Propranolol and bupranolol (nonselective beta-antagonists) antagonized, with a low potency, the effect of BRL 37344, whereas the beta 1-antagonist CGP 20712A and the beta 2-antagonist ICI 118551 were without action. CGP 20712A inhibited the effect of lower concentrations of agonists (0.05 microM isoproterenol, 0.1 microM norepinephrine and 0.1 microM procaterol) with an inhibitory constant (mean Ki) of 0.0075, 0.032 and > 10 microM, respectively. Mean Ki values for the beta 2-antagonist ICI 118551 were 1.744, 1.243, and 0.019 microM. This result indicates that low concentrations of isoproterenol and norepinephrine stimulate lipolysis mainly via beta 1-adrenoceptors in dog fat cells. Inversely, the lipolytic effect of higher concentrations of agonists i.e., 1 microM isoproterenol and catecholamines, was weakly antagonized by CGP 20712A or ICI 118551 while the nonselective beta-antagonists bupranolol and propranolol suppressed the effects with the order of potency expected for a beta 3-adrenoceptor: bupranolol > propranolol. These data indicate 1) the presence of a functional beta 3-adrenoceptor that coexists with beta 1- and beta 2-adrenoceptors in dog fat cells; 2) a separation of the differential potencies of physiological amines in the activation of lipolysis through beta 1-, beta 2-, and beta 3-adrenoceptors; the lipolytic response initiated at low concentrations (submicromolar range) of norepinephrine is primarily mediated by the beta 1-adrenoceptor subtype; and 3) an activation of the beta 3-adrenoceptor that occurs at higher concentrations of catecholamines.

High concentrations of dopamine and epinephrine protect dopaminergic D2 receptors from inactivation by phenoxybenzamine on primary cultured rat lactotrophs.

The effect of a high concentration of catecholamines on phenoxybenzamine pretreatment was examined. The efficacy of the pretreatments was monitored by testing the inhibitory action of dopamine on prolactin release. Phenoxybenzamine is a beta-haloalkylamine which alkylates and irreversibly inactivates adrenergic alpha-receptors in smooth muscle. Dopaminergic D2 receptors share several common characteristics with the alpha-receptors. Primary cultured male rat pituitary cells were used. After phenoxybenzamine (0.1 mumol/l) pretreatment, the inhibitory action of dopamine on prolactin release was significantly reduced in a perifusion system. When the cells were pretreated with phenoxybenzamine in medium containing 0.1 or 1 mmol/l dopamine, the 0.1-mmol/l dopamine did not change the effect of phenoxybenzamine on inactivation of the receptors, but the 1-mmol/l dopamine eliminated the effect of phenoxybenzamine pretreatment. These observations were confirmed with a static monolayer culture system. The observations illustrate that a high concentration of dopamine forms a D2 receptor-dopamine complex and protects the D2 from inactivation by phenoxybenzamine. When the cells were pretreated with 0.1 mumol/l phenoxybenzamine in a medium containing 1 mmol/l epinephrine, the effect of the phenoxybenzamine was also eliminated, suggesting that a sufficient amount of D2 receptor-epinephrine complex was formed to protect the receptor from inactivation. The hormone release in response to a secretagogue depends on its affinity and intrinsic activity. It is, therefore, suggested that the intrinsic activity of epinephrine is much lower than that of dopamine on prolactin release, since the D2 receptor-epinephrine complex is as stable as the D2 receptor-dopamine complex, and the inhibitory action of epinephrine on prolactin release is less than 10% of that of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic pharmacology in rats harboring pheochromocytoma.

Hypertension and cardiomyopathy are prominent findings in both humans and rats harboring pheochromocytomas, tumors that secrete enormous quantities of catecholamines in an unregulated fashion. We used New England Deaconess Hospital rats harboring pheochromocytomas to investigate the effects of chronic exposure to high concentrations of catecholamines on desensitization of alpha- and beta-adrenergic receptor-mediated responses activated by catecholamines. In addition, rats harboring pheochromocytomas provide a useful model to investigate catecholamine-induced hypertension and cardiomyopathy.

Hypertensive Crisis from Chronic Intoxication with Nasal Decongestant and Cough Medications

Cardiac hypertensive structural changes, catecholamine-related cardiomyopathy, and congestive heart failure (CHF) have been encountered in pheochromocytoma, as a result of prolonged exposure to high concentrations of endogenous catecholamines. A 34-year-old man presented with severe hypertension, cardiomegaly, and CHF, presumably as a result of continuous alpha-adrenergic intoxication with oxymetazoline hydrochloride, phenylephrine hydrochloride, and ephedrine hydrochloride, consumed in massive doses by an overuse of nasal decongestants and cough syrup (daily doses of 20, 100, and 300 mg, respectively). Coadministered chlorpromazine hydrochloride and trimeprazine tartrate may have also contributed to the clinical presentation through their anticholinergic and antihistaminic properties. The possibility of an overuse of these over-the-counter drugs should be considered in the differential diagnosis of hypertensive emergencies, especially with the simultaneous use of anticholinergic and antihistamine medications, beta-blocking agents, or monoamine oxidase inhibitors.

Catecholamines and related o-diphenols in cockroach hemolymph and cuticle during sclerotization and melanization: comparative studies on the order Dictyoptera

Catecholamines and related o-diphenols extracted from the cuticle and hemolymph of adult cockroaches during sclerotization and pigmentation of the cuticle were analyzed by reverse phase HPLC with electrochemical detection. At ecdysis, dopamine (DA) o-conjugates predominated in the hemolymph of Periplaneta americana, P. australasiae, P. fuliginosa, P. brunnea, and Blatta orientalis (Blattidae); Blattella germanica (Blattellidae); and Gromphadorhina portentosa and Blaberus craniifer (Blaberidae). N-Acetyldopamine (NADA) conjugates were second in abundance in these species, but were major in the hemolymph of the other blaberoid species, Leucophaea maderae and Nauphoeta cinerea. After ecdysis NADA became the major hemolymph catecholamine in all species as DA decreased rapidly. N-beta-Alanyldopamine (NBAD) concentrations in the hemolymph remained low in all species, although NBAD and its metabolite, N-beta-alanylnorepinephrine (NBANE), were generally the major catecholamines in tanning cuticle. Catechol (1,2-dihydroxybenzene) occurred mainly as a conjugate(s) at high levels in the hemolymph of nymphs and adults of all blattid species. Only trace amounts were detected in B. germanica and Cryptocercus punctulatus (Cryptocercidae), and none was found in any of the blaberoid species. High concentrations of NBANE and NBAD accumulated in tanning cuticle of B. germanica, G. portentosa, and all blattid species, whereas NADA and DA predominated in cuticle from the other blaberoid species, particularly L. maderae and N. cinerea. However, cockroaches as a group appear to utilize both the N-acetyl and N-beta-alanyl catecholamines for stabilization of the exoskeleton. The Blattidae differed most from the other families in having considerably higher concentrations of catecholamines in hemolymph and cuticle, as well as the large amounts of catechol conjugates in the hemolymph.

High concentrations of catecholamines in human hypothalamic-hypophysial blood.

While the hypothalamic-hypophysial portal system has been extensively studied in laboratory animals, equivalent studies have not been performed in humans. Here, we present an experimental procedure for collecting suprapituitary blood in man. To solve the question on the origin of such blood we investigated specific markers of hypothalamic secretory activity: the catecholamines (CAs). We found (a) norepinephrine (NE), dopamine (DA), and epinephrine (E) concentrations from approximately 1.5 to 2.5, 3.5 to 4.5, and 6- to 10-fold higher, respectively, in suprapituitary than peripheral blood, (b) different NE/DA and NE/E ratios in favor of DA and E in suprapituitary blood, and (c), a complete (100%) group separation (suprapituitary vs. peripheral) when discriminant analysis included only DA and E. These data indicate that suprapituitary blood composition is different from that of the peripheral blood, and is particularly rich in CAs and claimed differences between DA and E release on one hand and NE release on the other in suprapituitary blood also are observed. We advance the hypothesis of a hypothalamic source of such amines draining via median eminence into portal vasculature, and name this blood "hypothalamic-hypophysial blood." Besides serving as "classical" neurotransmitters, CAs may also have a direct neurohormonal role in the regulation of the human hypothalamic-hypophysial function.

Desensitization of alpha-1 adrenergic receptor mediated smooth muscle contraction in aorta from endotoxic rats

Desensitization of vascular smooth muscles in endotoxemia was studied using the aorta from intraperitoneally endotoxin-injected rats. The KCl- and phenylephrine-induced contractions were significantly decreased in the endotoxic aorta compared to the control. In the endotoxic aorta the phenylephrine-induced contracture showed a gradual tension decrease after reaching a plateau and was attenuated by prior exposure to high concentration of phenylephrine, while KCl produced a sustained contraction and it was not affected by prior exposure to phenylephrine. The phenylephrine- and KCl-induced contractures of the control aorta showed stable plateaus and were not affected by prior exposure to phenylephrine. Neither diminished contractile force nor in vitro desensitization of phenylephrine contracture of isolated aorta was prevented by pretreatment of endotoxic rats with an alpha-adrenergic antagonist, phentolamine. These findings suggest that the contractile response to phenylephrine is easily desensitized in the endotoxic aorta compared to the control and neither this in vitro desensitization nor the diminution of contractile force is caused by in vivo exposure of aorta to a high concentration of catecholamines during endotoxemia.

Neuroendocrine activation after acute myocardial infarction.

The extent of neuroendocrine activation, its time course, and relation to left ventricular dysfunction and arrhythmias were investigated in 78 consecutive patients with suspected acute myocardial infarction. High concentrations of arginine vasopressin were found within six hours of symptoms, even in the absence of myocardial infarction (n = 18). Plasma catecholamine concentrations also were highest on admission, whereas renin and angiotensin II concentrations rose progressively over the first three days, not only in those with heart failure but also in patients with no clinical complications. Heart failure, ventricular tachycardia, and deaths were associated with extensive myocardial infarction, low left ventricular ejection fraction, and persistently high concentrations of catecholamines, renin, and angiotensin II up to 10 days after admission, whereas in uncomplicated cases concentrations had already returned to normal.

Effects of anoxia and ischemia on uptake 2 of catecholamines in perfused rat heart

The effects of 30 min periods of either anoxia or ischemia (stop-flow) on the uptake 2 of isoprenaline and on the production of O-methyl-isoprenaline, a major metabolite of isoprenaline formed by catechol-O-methyltransferase (COMT), were examined in the perfused rat heart. After either glucose deprivation or anoxia, the uptake 2 of isoprenaline in hearts subsequently perfused with isoprenaline and 3′,4′-dihydroxy-2-methyl-propiophenone, a COMT inhibitor, was similar to control values. However, uptake 2 was decreased following either anoxia in association with glucose deprivation or ischemia. In the absence of the COMT inhibitor, neither glucose deprivation nor anoxia alone had any effect on the production of [ 3H]3-O-methyl-isoprenaline from [ 3H]isoprenaline, but both anoxia together with glucose deprivation and stop-flow ischemia decreased it. These findings indicate that both anoxia coupled with glucose deprivation and ischemia inhibit both uptake 2 and COMT activity and suggest that such inhibition may be responsible for the high concentration of catecholamines released locally following myocardial infarction.

Adenosine triphosphate stimulates inositol phospholipid metabolism and prostacyclin formation in adrenal medullary endothelial cells by means of P2-purinergic receptors.

In the adrenal medulla, chromaffin cells secrete high concentrations of catecholamines, ATP, peptides and other factors that must pass through an endothelial cell barrier to enter the bloodstream. We have measured the effect of several of these chromaffin cell secretory products on cultured bovine adrenal medullary endothelial cells and have found that only ATP stimulates prostacyclin formation. The stimulation of prostacyclin formation by ATP coincides with the metabolism of inositol phospholipids and the accumulation of the putative second messenger inositol trisphosphate. The time course, concentration dependence, and P2-purinergic receptor specificity were similar for ATP-stimulated prostacyclin formation and ATP-stimulated inositol phospholipid metabolism. Thus, the increase in prostacyclin formation may be secondary to mobilization of intracellular Ca2+ by inositol trisphosphate, leading to activation of phospholipase A2, liberation of arachidonic acid, and the conversion of arachidonic acid to prostacyclin. We propose that the function of ATP, which is often colocalized with cell-specific hormones in secretory cells, may be to regulate blood flow in the adrenal medulla and other endocrine tissues by interacting with adjacent endothelial cells.

Estimation of catecholamine potencies on the myocardium by means of a new method.

A simple method is described for evaluating the potencies of catecholamines on the slow response of myocardium. Catecholamines depolarize guinea pig ventricular muscle cells exposed to the high K+ (27 mmol/l) Tyrode's solution containing 0.2 mmol/l Ba through an increase in slow channel conductance. Higher concentrations of catecholamines in addition induce spontaneous action potentials. This model was used to estimate and compare catecholamine potencies on myocardium. Catecholamine concentrations needed for depolarization alone or for depolarization plus automatic activity were taken as basis for comparison. The order of potency obtained by means of this new method was: l-isoproterenol greater than l-adrenaline greater than or equal to dl-noradrenaline greater than or equal to dobutamine greater than or equal to dopamine. This is similar to the order reported with other methods.

Beta-adrenoceptor function in white blood cells from newborn infants: no relation to plasma catecholamine levels.

The maturity of beta-adrenoceptors in newborn infants was studied in relation to the catecholamine surge during labor. Umbilical blood was collected at birth from 12 infants delivered vaginally and 13 infants delivered by elective cesarean section. Granulocytes and lymphocytes were isolated. Receptor numbers and binding affinity were determined in the granulocytes by incubation with 125I-iodohydroxybenzylpindolol. Receptor responsiveness was tested by assessing isoproterenol-induced cyclic AMP accumulation in lymphocytes. Significantly higher plasma noradrenaline, adrenaline, and dopamine concentrations were found in infants born vaginally (108; 8.9; 0.9 nmol/liter, liter, respectively, median values) as compared with those delivered by cesarean section (11.0; 2.4; 0.2 nmol/liter). No significant differences in beta-adrenoceptor binding sites (receptor number: 39.2 +/- 2.6 versus 44.7 +/- 5.9 fmol/mg protein and binding affinity: 66.6 +/- 7.8 versus 65.0 +/- 6.2 pM) or responsiveness (maximal isoprenaline induced cAMP formation 52.4 +/- 10.3 versus 40.6 +/- 8.9 pmol/10(6) cells) were found between the two groups of infants. Lymphocyte beta-adrenoceptor sensitivity was similar to that found in adults. The beta-adrenoceptors on whole blood cells seem to be mature at birth and have the same responsiveness as in adults. The higher catecholamine surge during vaginal delivery as compared to elective cesarean section does not seem to affect beta-adrenoceptor function. Our results do not support the idea that reduced beta-adrenoceptor function is the cause of the previously observed inappropriately small cardiovascular and metabolic responses to the exceptionally high plasma catecholamine concentrations at birth.

High concentrations of catecholamines selectively diminish the sensitivity of CRF-stimulated acth release by cultured rat pituitary cells to the suppressive effects of dexamethasone

ACTH-release by primary cultures of rat anterior pituitary cells in response to CRF, vasopressin, epinephrine, norepinephrine and VIP is readily suppressible by dexamethasone. Rat hypothalamic extract-induced ACTH release is less sensitive to the inhibitory effect of dexamethasone than that elicited by CRF and the other secretagogues mentioned above. In studying the additive and potentiating effect on ACTH release of CRF in combination with vasopressin, VIP and the catecholamines it became evident that only the combination of micromolar concentrations of epinephrine or norepinephrine together with nanomolar concentrations of CRF will make ACTH release significantly less sensitive to the suppressive effect of dexamethasone. Other combinations of CRF and vasopressin or CRF and VIP will render ACTH release as suppressible to dexamethasone, as that elicited by each of these compounds by itself. This observation in the rat might explain at least in part the observation that a diminished suppressibility of the pituitary-adrenal axis ti dexamethasone can be found in patients with psychiatric disease, especially depression.