Response In Intact Rats Research Articles

Activation of the Galanin Receptor 2 in the Periphery Reverses Nerve Injury-Induced Allodynia

BackgroundGalanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain.ResultsExogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord.ConclusionsThese findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.

NS11021, a novel opener of large‐conductance Ca2+‐activated K+ channels, enhances erectile responses in rats

Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)), located on the arterial and corporal smooth muscle, are potential targets for treatment of erectile dysfunction (ED). This study investigated whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea), a novel opener of BK(Ca) channels, relaxes erectile tissue in vitro and enhances erectile responses in intact rats. The effects were compared with sildenafil, an inhibitor of phosphodiesterase type 5. Patch clamp was used to record whole cell current in rat isolated corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs). Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from rats and men, and simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were performed in intracavernous arteries. Erectile response was measured in anaesthetized rats. In patch clamp recordings, NS11021 increased currents sensitive to the selective BK(Ca) channel blocker, iberiotoxin (IbTX) in SMCs, but did not modulate K(+) current in HUVECs. NS11021 reduced [Ca(2+)](i) and tension in penile arteries. IbTX inhibited the vasorelaxation induced by NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not vehicle increased erectile responses in anaesthetized rats, an effect which was abolished after pretreatment with tetraethylammonium. NS11021 leads to relaxation of both intracavernous arteries and corpus cavernosum strips primarily through opening of BK(Ca) channels. It is also effective in facilitating erectile responses in anaesthetized rats. These results suggest a potential for use of BK(Ca) openers in the treatment of ED.

Behavioral effects of dehydroepiandrosterone in adult male rats

It is well-documented that dehydroepiandrosterone (DHEA) exhibits various behavioral effects in rodents, at least one of which is modulation of learning/memory processes in several test paradigms. However, little is known about the influence of DHEA on cognitive performance in the adult rodents. This work was designed to determine whether chronic DHEA administration during 10 days in the high (0.7 mg/kg, s.c.) or low (0.1 mg/kg, s.c.) doses has any effect on learning/memory abilities and behavior in the adult male rats (5- to 6-month old). Effect of DHEA was estimated in active and passive avoidance tasks, behavior was registered in the elevated “plus” maze and the “open field” test. DHEA in the high dose significantly ( p<0.05) increased time spent and the number of enterings in the “open” arms of the elevated “plus” maze in intact male rats as compared with the control rats. DHEA in the low dose significantly ( p<0.05) decreased horizontal and vertical locomotor activity and grooming behavior, whereas DHEA in the high dose did not significantly modify behavior in intact rats as compared with control group. Results of the ANOVA on passive avoidance performance revealed no statistically significant differences among the groups receiving DHEA in the high or low doses as compared to the control. However, DHEA in the low dose significantly ( p<0.05) reduced the number of correct avoidance responses in intact rats as compared to the control rats, while in rats treated with the high dose DHEA, the active avoidance performance did not differ significantly from the control. Thus, chronic DHEA administration has a modulatory action on the learning and behavior of the adult male rats.

Effect of acute nitric oxide synthase inhibition in the modulation of heart rate in rats.

Acute nitric oxide synthase inhibition with N G-nitro-L-arginine methyl ester (L-NAME) on chronotropic and pressor responses was studied in anesthetized intact rats and rats submitted to partial and complete autonomic blockade. Blood pressure and heart rate were monitored intra-arterially. Intravenous L-NAME injection (7.5 mg/kg) elicited the same hypertensive response in intact rats and in rats with partial (ganglionic and parasympathetic blockade) and complete autonomic blockade (38 +/- 3, 55 +/- 6, 54 +/- 5, 45 +/- 5 mmHg, respectively; N = 9, P = NS). L-NAME-induced bradycardia at the time when blood pressure reached the peak plateau was similar in intact rats and in rats with partial autonomic blockade (43 +/- 8, 38 +/- 5, 46 +/- 6 bpm, respectively; N = 9, P = NS). Rats with combined autonomic blockade showed a tachycardic response to L-NAME (10 3 bpm, P<0.05 vs intact animals, N = 9). Increasing doses of L-NAME (5.0, 7.5 and 10 mg/kg, N = 9) caused a similar increase in blood pressure (45 +/- 5, 38 +/- 3, 44 +/- 9 mmHg, respectively; P = NS) and heart rate (31 +/- 4, 34 +/- 3, 35 +/- 4 bpm, respectively; P = NS). Addition of L-NAME (500 micro M) to isolated atria from rats killed by cervical dislocation and rats previously subjected to complete autonomic blockade did not affect spontaneous beating or contractile strength (N = 9). In vivo results showed that L-NAME promoted a tachycardic response in rats with complete autonomic blockade, whereas the in vitro experiments showed no effect on intrinsic heart rate, suggesting that humoral mechanisms may be involved in the L-NAME-induced cardiac response.

Serotoninergic and suprachiasmatic nucleus involvement in the corticotropic response to systemic endotoxin challenge in rats.

We have investigated whether the serotonin system participates in the mechanisms underlying the corticotropic response in experimentally infected rats. Intra-arterial injection of lipopolysaccharide (LPS; 25 microg/kg b.w.) resulted in a slight but significant increase in serotonin (5-HT) metabolism, detectable 60 min after the stimulus and lasting more than 480 min. Adrenocorticotropin (ACTH) and corticosterone (CORT) responses in intact rats conformed to earlier reports, increasing as early as 30 min after LPS injection and reaching maximal concentrations in the circulation 60 min after the bacterial endotoxin injection. Plasma concentrations of interleukin-1beta (IL-1beta) increased only after 60 min, reaching maximal levels 120 min after LPS. Depletion of hypothalamic 5-HT (-93%) by pretreatment of the animals with para-chlorophenylalanine (p-CPA), resulted in a halved ACTH response to LPS, despite an overall unchanged secretory pattern. Neither CORT nor IL-1beta secretory patterns were affected in these rats pretreated with p-CPA. Complete bilateral electrochemical lesions of the suprachiasmatic nucleus (SCN), which is innervated by mesencephalic 5-HT, impaired the early phase of the ACTH (-75% at 30 min) and CORT (-40% at 30 min) responses but did not affect the later increases of the corticotropic and the plasma IL-1beta responses following the LPS injection. These results indicate that serotonin pathways and SCN are involved in the earlier mechanisms of corticotropic axis recruitment following systemic LPS endotoxemia.

Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat.

Castration of adult male rats reduces by half the penile erectile response to electrical field stimulation (EFS) of the cavernosal nerve, and the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whether other strategies of androgen ablation or competition may act as stronger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left intact and were treated daily as follows: 1) intact, with the antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via silastic tubing, s.c.). Additional groups of intact rats received injections of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios between maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were determined. Castration reduced the MIP:MAP ratio and penile NOS activity. Androgen receptor blockade with flutamide induced a similar response in intact rats. When flutamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the values in castrated rats. Estradiol given to castrated rats and hypophysectomy or GnRHA treatment in intact rats diminished the erectile response below the level in castrated animals. In hypophysectomized rats, penile NOS activity fell below levels in castrated animals. contents of nNOS and eNOS were not significantly reduced by any treatment. These data suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of penile NOS activity and of other ancillary factors. However, only the complete blockade of residual androgen effects at the tissue level or a total androgen depletion can abolish the erectile response.

Sympathoadrenal system in stress. Interaction with the hypothalamic-pituitary-adrenocortical system.

Exposure of an organism to any of a variety of stressors markedly activates the sympathoadrenal and hypothalamic-pituitary-adrenocortical systems. Interactions of these major stress systems occur at several levels in the periphery and the brain. In the present study, we used sham-operated or adrenalectomized cortisol-treated conscious rats to examine glucocorticoid effects on indices of CA release, metabolism, and synthesis, and on CA biosynthetic enzyme activities and gene expression at baseline and during immobilization stress (IMO). Adrenalectomy (ADX) stimulated basal and stress-induced increments in norepinephrine release, reuptake, metabolism, turnover, and biosynthesis. Loss of adrenomedullary hormones after ADX did not appear to contribute to these increments. Cortisol treatment reversed the ADX effects on CA indices and suppressed catecholaminergic responses to IMO in intact rats. These results suggest that endogenous glucocorticoids restrain responses of catecholamine turnover, synthesis, release, reuptake, and metabolism during stress. In contrast, in intact rats, continuous administration of cortisol lasting for 7 days exaggerated the IMO-induced increases in plasma CA levels. Inhibition of DOPA conversion to dopamine elevated plasma DOPA levels in chronically cortisol-treated stressed rats compared to saline-treated ones, suggesting a cortisol-induced increase in tyrosine hydroxylation. Stress increases TH and PNMT activities and mRNA levels in the adrenal medulla. Hypophysectomy reduced adrenal PNMT but not TH mRNA levels in control and IMO rats. Pretreatment of hypophysectomized animals with ACTH fully restored the control and IMO-induced adrenal PNMT mRNA levels and augmented PNMT but not TH mRNA responses in intact rats. Long-term cortisol administration to intact rats also elevated adrenal PNMT but not TH mRNA levels. The results indicate a suppressive effect of endogenous glucocorticoids and a stimulatory effect of chronically elevated glucocorticoid levels on sympathoadrenal activity during stress. The results also suggest that a nonneuronal, nonpituitary factor contributes to TH gene expression during some forms of stress, whereas pituitary-adrenocortical factors play the essential role in the regulation of PNMT gene expression.

Cardiac baroreflex dynamics during the defence reaction in freely moving rats

To determine the extent of baroreceptor reflex involvement in the cardiovascular changes observed during electrically induced defence reaction, the mean arterial blood pressure (MBP) and heart rate (HR) of conscious intact or sinoaortic baroreceptor denervated (SAD) rats were continuously recorded from indwelling cannulae during a 1-min period of electrical stimulation of the mesencephalic tectum. Electrical stimulation produced stimulus intensity-dependent behaviours including freezing at lower intensities and flight at higher intensities. The cardiovascular responses in intact rats were dependent on both the intensity and duration of the stimulus. A linear increase in MBP was observed with increasing stimulus intensities. However, while a slight bradycardia was observed during the freezing behaviour, a marked tachycardia occurred during flight. Simultaneous increases of MBP and HR were seen throughout the first 15 s of the flight response, after which the HR rapidly fell to baseline levels, whereas the MBP remained at a hypertensive plateau until the end of the stimulus. The baroreflex HR curve showed a parallel shift to the left during the first half of the freezing period, being fully reset 40 s after that. So, while the baroreflex gain remained unchanged, the reflex set point was lowered during the freezing stage of the defence reaction. The experiments with SAD rats corroborated the above data. The baroreceptor denervation reversed the freezing bradycardia to tachycardia. Moreover, the denervation potentiated the flight tachycardia and prevented its later reset. MBP responses of baroreceptor denervated rats did not differ from the sham-operated group. The sustained hypertension, thus, appears to be mediated by mechanisms other than the mere baroreceptor reflex deactivation. In summary, our data suggest that the baroreflex inhibition seems to be both partial and transient during the defence reaction induced by the electrical stimulation of the rat mesencephalic tectum.

Sympathoadrenal Mechanisms Underlying Cardiovascular Responses to Intrathecal Substance P in Conscious Rats

The sympathoadrenal mechanisms underlying cardiovascular responses to intrathecal (i.th.) injection of substance P (SP), at the T-9 spinal level, were investigated in conscious rats. Release of norepinephrine (NE), and epinephrine (EPI) could be induced by 6.5, 16.25, and 32.5 nmol SP correlated with a pressor and a positive chronotropic response. Release of neuropeptide Y (NPY) was evoked also by 32.5 nmol SP, and released NPY appears to derive from the adrenal medulla. The initial pressor response in intact rats is mediated by NE from sympathetic fibers, whereas the latent pressor response, observed in sympathectomized rats, is possibly due to NPY from the adrenal medulla. Although a functional balance between the sympathetic fibers and the adrenal glands is supported by the results, it appears that only the tachycardia can be efficiently produced by the adrenals in the absence of the sympathetic fibers. This study supports a functional role for SP in regulation of the sympathoadrenal system at the spinal level.

Penile erection in the rat: Stimulation of the hypogastric nerve elicits increases in penile pressure after chronic interruption of the sacral parasympathetic outflow

Penile erection, a vascular event mediated by the autonomic nervous system, is often adversely affected by injury to the spinal cord. To further characterize the laboratory rat as an animal model of penile erection and to investigate erectile responses following neural injury, the present study has examined pressor penile responses in intact rats and in animals deprived of sacral parasympathetic outflow. Increases in penile pressure result from graded stimulation of postganglionic parasympathetic fibers. The vasodilator response is insensitive to blockade with atropine, a cholinergic antagonist. Penile tumescence also results from stimulation of the pelvic nerve, but not the hypogastric nerve. However, beginning 3 days after unilateral interruption of the pelvic nerve, stimulation of the ipsilateral hypogastric nerve results in an increase in penile pressure. This novel response, which is blocked by a ganglionic antagonist, is maximally developed at 1 week post-lesion, is stable for at least 3 months and remains confined to the side of the lesion. These results suggest that the rat, although relatively small, can be used to obtain quantitative data on penile erection. Moreover, the model may lend itself to an analysis of the mechanisms of altered control of visceral tissues following injury to the nervous system.

Differential Response of Lactotrophs and Somatotrophs to a Joint Application of Vasoactive Intestinal Peptide and Thyrotrophin‐Releasing Hormone in the Rat

Abstract We have studied the responses of growth hormone, prolactin and thyrotrophin to vasoactive intestinal peptide and thyrotrophin-releasing hormone added either together or separately under various in vivo (free-moving, intact animals or rats bearing hypothalamic lesions) or in vitro (perifused anterior pituitary fragments) conditions. Thyrotrophin-releasing hormone or vasoactive intestinal peptide stimulated prolactin release in all cases and the individual effects of both peptides were additive when administered together. Vasoactive intestinal peptide, but not thyrotrophin-releasing hormone, induced a growth hormone response in intact rats. In contrast, both peptides stimulated growth hormone release in lesioned rats as well as in perifused anterior pituitary fragments. In that case, the effect of vasoactive intestinal peptide on growth hormone release was not additive with that of thyrotrophin-releasing hormone, either in vivo or in vitro. Thyrotrophin release was slightly stimulated by vasoactive intestinal peptide, whereas it responded markedly to thyrotrophin-releasing hormone. The effect of thyrotrophin releasing-hormone was not further affected by simultaneous vasoactive intestinal peptide administration. These data suggest that additivity of the effect of second messengers generated as a response to thyrotrophin-releasing hormone and vasoactive intestinal peptide are specific of the target cell type.

The Possible Role of Atrial Natriuretic Factor in Modulating the Pulmonary Hypertensive Response to Hypoxia

Atrial natriuretic factor (ANF) is a 28 amino acid peptide that is released by cardiac atria in response to distention or pressure elevation.1 In addition to its natriuretic and diuretic actions, ANF is a vascular smooth muscle relaxant and blunts hypoxic vasoconstriction when administered exogenously to dogs.2 We hypothesized that increased release of ANF from stretched cardiac atria might play a role in modulating pulmonary hypertensive responses to acute and chronic hypoxia. We first measured changes in rat plasma ANF levels in response to acute hypoxia and determined whether similar levels were capable of blunting hypoxic pressor responses in intact rats.

Interactions of cholecystokinin, beta-endorphin, and their antagonists on passive avoidance behavior in rats.

The effects of cholecystokinin octapeptide (CCK-8), cholecystokinin tetrapeptide amide (CCK-4), beta-endorphin, proglumide, and naloxone on passive avoidance behavior were studied in rats. Intracerebroventricular (i.c.v.) injection of beta-endorphin (1-10 micrograms) had no significant influence on the latency of the avoidance response in intact rats. Also, beta-endorphin (0.05-5 micrograms, i.c.v.) did not affect the response in rats treated with electroconvulsive shock (ECS). The preventive effect of CCK-8 (0.1-1.0 micrograms, i.c.v.) on ECS-induced amnesia was partly antagonized by beta-endorphin (0.05-10 micrograms, i.c.v.). Intraperitoneal (i.p.) injection of naloxone (1-10 mg/kg) could not prevent ECS-induced amnesia, but continuous subcutaneous infusion of this drug (2 mg/day, 7 days) completely abolished the amnesia. Naloxone (1 and 10 mg/kg, i.p.) also partly antagonized amnesia induced by proglumide (1 and 10 micrograms, i.c.v.) and prevented it when induced by CCK-4 (5 and 10 micrograms, i.c.v.). The results indicate the facilitating action of naloxone and the inhibitory effect of beta-endorphin on memory, suggesting that the endogenous opiate systems are involved in some way in the memory processes.

Ｙ‐８８９４の薬理学的研究（第５報） 正常および実験的記憶障害動物の学習および記憶に対する作用

The effects of Y-8894 on learning and memory were studied using the pole climbing avoidance (PCA) response in intact and experimentally induced amnesic rats. The following results were obtained: A single administration of Y-8894 (2.5 mg/kg, i.p.) to experimentally induced amnesic rats significantly antagonized the decrease in the mean number of PCA responses induced by an electroconvulsive shock (ECS). At a higher dose (10 mg/kg, i.p.), however, this effect was reduced. Repeated administration of Y-8894 (5 mg/kg, i.p.) significantly antagonized the facilitation of the extinction of the PCA response induced by exposure to CO2. Repeated administration of Y-8894 (2.5 mg/kg, i.p.) significantly facilitated the learning of the PCA response in intact rats. At a higher dose (5 mg/kg, i.p.), however, this effect was reduced. A single administration of Y-8894 (5 mg/kg, i.p. and 25 mg/kg, p.o.) significantly delayed the extinction of the PCA response in intact rats. These results suggest that Y-8894 has an ameliorative and facilitative effect on learning and memory in experimentally induced amnesic and intact rats.

The role of spinal pathways in dopamine mediated alteration in the tail-flick reflex in rats

The latency of the tail-flick, following intrathecal infusion of the dopamine (DA) agonist, R-apomorphine was measured in rats with intact spinal cord or with spinal cord lesions. Apomorphine failed to influence the tail-flick response in intact rats, whereas it elevated the latency of the tail-flick in rats with either total spinal cord transection, or bilateral lesions of the dorsolateral funiculi (DLF), but not in rats with lesions in either the dorsal columns or the medioventral parts of the lateral funiculi. The findings suggest that pathways in the dorsolateral funiculi modulate DA-mediated sensory processes and possible mechanisms are discussed.

Electrophysiological studies on plasticity of cerebellothalamic neurons in rats following neonatal hemicerebellectomy.

Changes in the cerebello-thalamo-cerebral projection following hemicerebellectomy were investigated in 16 rats by laminar field potential analysis of cerebello-cerebral responses in the cerebral cortex and by unitary recording of antidromic responses of cerebellar nuclear neurons to stimulation of the thalamus. In contrast to the occurrence of an exclusively contralateral cerebello-cerebral response in intact rats, a significant bilateral cerebello-cerebral response could be evoked in all 8 rats hemicerebellectomized before 6 days of age (early hemicerebellectomy). On the other hand, in all 5 rats operated on at 8 to 15 days of age (late hemicerebellectomy) and in the 3 rats operated on in adulthood, the cerebello-cerebral response was evoked only contralaterally just as in intact rats. Unitary recordings of antidromic responses of cerebellar nuclear neurons revealed that bilateral or ipsilateral cerebellothalamic projection neurons were remarkably more numerous in early hemicerebellectomized rats than in controls (P less than 0.001). Such neurons were less frequently found in late hemicerebellectomized rats, but they were still more numerous than in controls (P less than 0.005). Absence of the ipsilateral cerebello-cerebral response in late hemicerebellectomized rats indicates that even though bilateral or ipsilateral cerebellothalamic projection neurons may exist in these rats more numerously than in intact rats, they may not be sufficient in number or in efficiency to mediate a detectably response.

Coupling of signals to brown fat: alpha- and beta-adrenergic responses in intact rats.

The present study examines the effects of alpha- and beta-adrenergic antagonists (phentolamine and propranolol, respectively) and agonists (phenylephrine, isoproterenol) on the neurally induced temperature changes and membrane potentials of interscapular brown adipocytes. These studies, performed in vivo with anesthetized rats, indicate that both alpha- and beta-adrenergic components are associated with the biphasic temperature changes observed following sympathetic activation of the tissue. Specifically, the initial transient temperature decrease seen after brown fat stimulation appeared to reflect vasoconstriction mediated primarily via alpha-receptors, while the subsequent rise in tissue temperature was associated primarily (though perhaps not entirely) with beta-adrenergic pathways. In contrast, the redistribution of ions across the membrane of the brown adipocyte, a phenomenon manifested as a membrane depolarization, was elicited by phenylephrine (an alpha-agonist) as well as by isoproterenol (a beta-agonist), with the magnitude of the isoproterenol-induced depolarization being comparable to that of the phenylephrine-induced effect.

Brain Serotonin and Pituitary-Adrenal Function

Publisher Summary This chapter describes the serotonin (5-HT) and pituitary-adrenal function. The effects of altering 5-HT synthesis on the diurnal rhythm of plasma corticosterone and on the pituitary adrenal response to stress were studied in rats and man. The hypothesis is proposed that 5-HT mediates the corticosteroid negative feedback mechanism that regulates corticotrophin (ACTH) secretion and that the primary site of this feedback is extra hypothalamic. In contrast, pretreatment with I-tryptophan, 5-HTP alone or 5-HTP and MK 486 reduced slightly the stress response in intact rats and 5-HTP with MK 486 reduced 24 h urinary 17-hydroxycorticosteroids (17-OHCS) excretion in humans. On the other hand corticosterone administration or stress increased the activity of tryptophan hydroxylase in the midbrain and the conversion of tryptophan to 5-HT. In addition, there appears to be a correlation between the daily rhythm of 5-HT content in the limbic system and that of circulating corticosterone. It is reported that treatment with parachlorophenylalanine (PCPA) abolished the diurnal variation of plasma corticosterone at an intermediate level in the rat, affect the metabolism or action of 5-HT abolished the daily rise in plasma 17-OHCS in the cat but did not block the response to stress.

Unique Pituitary Peptides with Behavioral-affecting Activity

Publisher Summary This chapter highlights the unique pituitary peptides with behavioral-affecting activity. Initial screening studies for behavioral-affecting activity were performed on hypophysectomized rats. Four unique porcine pituitary peptides are isolated and partially characterized, which upon subcutaneous administration potently facilitate acquisition of conditioned avoidance responses in hypophysectomized rats and inhibit extinction of avoidance responses in intact rats. The profound deficit in acquisition and retention of conditioned avoidance responses (CARS) imposed on rats by hypophysectomy can be substantially reversed by subcutaneous administration of corticotrophin (ACTH) and certain subunits thereof, as well as by the melanotrophins and pitressin. The potent behavioral effects of synthetic corticotrophin subunits in conjunction with an apparent lack of peripheral action suggested the possible existence of naturally occurring pituitary peptides with similar biological activity. The availability of a porcine pituitary extract in a large quantity afforded the opportunity to undertake a search for such compounds.

Effect of vagotomy and-or antrectomy on gastric secretion stimulated by intravenous infusion of bethanechol chloride. Study on rats with gastric fistula.

The interdigestive phase of gastric secretion was investigated for 24 hr in rats bearing permanent gastric fistulas. Intact controls, vagotomized, antrectomized and vagotomized-antrectomized animals were studied. Vagotomy, alone or combined with antrectomy, abolished the secretory function of parietal and zymogenic cells during the spontaneous interdigestive phase of secretion. This was considered due to the fact that the interdigestive secretion is vagus dependent and represents a true cephalic phase. Antrectomy did not result in the decrease of spontaneous secretion of HCl or pepsin. Intra-arterial stimulation with a stable choline ester, bethanechol, produced adequate secretory response in intact rats and partially restored the function of parietal cells in vagotomized rats. The action of bethanechol on HCl secretion in antrectomized rats was less marked. However, bethanechol has a very marked stimulatory effect on the secretion of pepsin in intact, vagotomized and antrectomized rats. Sensitivity of gastric mucosa to bethanechol was nearly abolished in vagotomized-antrectomized rats.