Inhibitory effect of sorbin on pepsin secretion in conscious cats and rabbits

Sorbin, a 153 amino acid polypeptide isolated from porcine upper small intestine and its shortest synthetic derivative, the C-terminal heptapeptide (C7-sorbin), substituted by D alaninamide in the last position (D7-sorbin), have proabsorptive and antisecretory effect in the different parts of the intestine. We showed that labeled C7-sorbin accumulated not only in the enterocytes and the enteric nervous system but also in the gastric chief cells in the rat. The chief cell secretion of pepsin was then studied in two other species, the cat and the rabbit, simultaneously with the acid secretion of parietal cells. Lipase secretion was studied in the rabbit because lipase is exclusively secreted by the upper cells of the fundic glands, which do not secrete pepsin. The animals were equipped with a gastric fistula, fully innervated, and a Heidenhain pouch, vagally denervated, during a continuous perfusion of pentagastrin (PG) 2 microg/kg. h and vasoactive intestinal peptide (VIP) 4 microg/kg. h. D7-sorbin (100 pmol/kg. h) inhibited cat and rabbit pepsin secretion from the innervated gastric fistula secretion and from the cat denervated Heidenhain pouc secretion, but was without effect on acid secretion and lipase secretion. These data indicate that the inhibitory effect of sorbin is specific on chief cells because the acid parietal cell secretion in both species and lipase upper cell secretion of the fundic glands, in the rabbit, are not implicated.     

Effect of metoclopramide on prolactin secretion in man

Prolactin (PRL) secretion was studied after i.m. administration of Metoclopramide (alone or with a pretreatment with 5-Br-2alpha-ergo-cryptine) and after i.m. administration of Sulpiride. The results obtained evidenced a considerable hPRL increase after Metoclopramide administration, similar to that observed with Sulpiride, completely abolished by 5-Br-2alpha-ergocryptine. On the basis of these data it seems evident a strong and specific effect of Metoclopramide on hPRL secretion, probably more potent than Sulpiride.     

Somatostatin inhibits prolactin secretion in the estradiol primed male rat

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 microL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 micrograms/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.     

Effect of dexamethasone on plasma catecholamine levels of conscious dogs in haemorrhagic shock

After 15 mg/kg dexamethasone pretreatment, conscious dogs in haemorrhagic shock demonstrated an augmented plasma noradrenaline increase. Increasing early compensatory adrenergic neuroeffector response could be one of the mechanisms of the protective effect of steroids in shock.     

Effect of ergocristine on prolactin secretion in the male rat with pituitaries grafted beneath the kidney capsule.

Male rats in which three pituitaries were grafted beneath the kidney capsule showed approximately a fourfold increase in circulating plasma prolactin concentration. The elevated plasma prolactin concentration did not remain at a constant level but fluctuated with time. The elevated prolactin concentration declined immediately after a single bolus injection of ergocristine (30 micrograms/kg). The slope of the prolactin decay curve, determined by sequential blood sampling, was parallel to a theoretical slope having a 7-min half-life. This result indicates that ergocristine blocked prolactin secretion immediately and completely as the decay curve (T 1/2 = 6.5 min, confidence interval 4.5--11.3) resulting from the administration of ergocristine is the same as the endogenous prolactin decay curve (T 1/2 = 7 min).     

Basal plasma aldosterone levels and tetracosactid-induced increase of aldosterone secretion in conscious male rabbits: lack of correlation with glucocorticosteroid levels

The adrenocortical secretory activity under basal conditions and after treatment with tetracosactid (1-24ACTH) has been investigated in chronically cannulated male rabbits. Basal plasma concentrations of glucocorticosteroids (0.74 micrograms/100 ml) and aldosterone (78 pg/ml) have been determined in a greater number of animals. No significant positive correlation between basal glucocorticosteroid and aldosterone plasma levels could be found. After intravenous injection of 2.5, 5.0, 10.0 and 20.0 micrograms/kg body weight tetracosactid glucocorticosteroid concentrations were significantly elevated between 40--100 min after administration; aldosterone release, on the other hand, was significantly increased only after injection of 10.0 or 20.0 micrograms/kg body weight tetracosactid between 20--60 min after injection. After administration of high tetracosactid doses glucocorticosteroid and aldosterone plasma concentrations were significantly correlated (10.0 micrograms/kg: r = 0.62; 20.0 micrograms/kg: r = 0.26). Because of the relative insensitivity of the zona glomerulosa cells to tetracosactid administered intravenously, it is concluded that ACTH is only of minor importance in the regulation of aldosterone secretion in the rabbit.     

Effect of cysteamine on suckling-induced prolactin secretion in the rat

We have examined the effects of the thiol agent cysteamine on physiological prolactin secretion in the female rat. Administration of cysteamine completely abolishes suckling-induced prolactin secretion in a dose-dependent manner. Cysteamine treatment does not alter nursing behavior of the mothers. Further, we have found that the prolactin-depleting ability of cysteamine is not altered by a prior suckling stimulus. These results indicate that cysteamine administration inhibits physiologically-induced prolactin secretion with similar potency and efficacy as previously reported for cysteamine effects on basal and pharmacologically-induced prolactin secretion. Furthermore, the effect of cysteamine is not compromised by a previous suckling stimulus, suggesting that "depletion-transformation" of pituitary prolactin stores does not protect against the effect of cysteamine.     

Effect of metoclopramide-induced prolactin on aldosterone secretion in normal subjects

We investigated the role of prolactin (PRL) on modurating the secretion of aldosterone in normal male subjects. Metoclopramide (5mg) which causes a significant rise of PRL was given by intravenous injection. The peak of PRL level at 30 min. after i.v. injection of metoclopramide (20.0 ± 1.6 ng/ml, mean ± S.E.) was significantly higher than the basal level (6.4 ± 2.1 ng/ml, P < 0.01), but plasma aldosterone, serum sodium, potassium and plasma renin activity did not change significantly throughout the period of the study. Cortisol levels, however, reduced significantly after 30 min. and remained significantly low, probably because of diurnal variation. Present results suggest that PRL might at least not play a physiological role on regulating the secretion of aldosterone in man.     

Differential effects of dopamine antagonists on prolactin secretion from cultured rat pituitary cells.

Various dopamine antagonists, including two novel non-neuroleptic drugs domperidone and halopemide, stimulated apomorphine-suppressed prolactin secretion from cultured rat pituitary cells. The potency of these drugs closely paralleled their rank-order in displacing $\text{in vitro}$ H³-haloperidol binding in rat striatum reported by others (10). Concentration-effect curves were parallel except those of pimozide and clopimozide which were biphasic : prolactin secretion was stimulated at low concentrations but depressed at concentrations above 25nM. When added alone, pimozide and clopimozide, but none of the other drugs tested, also depressed prolactin secretion. The present findings indicate that prolactin secretion from cultured pituitary cells may provide an $\text{in vitro}$ test system suitable to differentiate antagonists of dopamine receptors and possibly to distinguish pure from partial antagonists.     

Effects of angiotensin II on autonomic components of nasopharyngeal stimulation in male conscious rabbits.

Angiotensin II (ANG II) is known to activate central sympathetic neurons. In this study we determined the effects of ANG II on the autonomic components of the cardiovascular responses to stimulation of nasopharyngeal receptors with cigarette smoke. Experiments were carried out in conscious New Zealand White rabbits instrumented to record arterial pressure and heart rate. Rabbits were exposed to 50 ml of cigarette smoke before and after subcutaneous osmotic minipump delivery of ANG II at a dose of 50 ng.kg(-1).min(-1) for 1 wk in one group and intracerebroventricular (icv) infusion at a dose of 100 pmol/min for 1 h in a second group. The responses were compared before and after heart rate was controlled by pacing. Autonomic components were evaluated by intravenous administration of atropine methyl bromide (0.2 mg/kg) and prazosin (0.5 mg/kg). ANG II given either systemically or icv significantly blunted the pressor response to smoke (P < 0.05) when the bradycardic response was prevented. This blunted response was not due to an absolute increase in baseline blood pressure after ANG II infusion (71.64 +/- 11.6 vs. 92.1 +/- 19.8 mmHg; P < 0.05) because normalization of blood pressure with sodium nitroprusside to pre-ANG II levels also resulted in a significantly blunted pressor response to smoke. The effect of smoke was alpha(1)-adrenergic receptor-mediated because it was essentially abolished by prazosin in both the pre- and the post-ANG II states (P < 0.05). These results suggest that elevations in central ANG II reduce the sympathetic response to smoke in conscious rabbits. This effect may be due to an augmentation of baseline sympathetic outflow and a reduction in reflex sensitivity similar to the effect of ANG II on baroreflex function.     

Inhibition of prolactin secretion and androgenic function in the adult male rat

The effects of bromocriptine induced hypoprolactinemia on the testicular function were studied in adult rats. Bromocriptine treatment (1500 micrograms/day for 24 days) reduced serum and pituitary Prolactin levels, indicating a decrease in prolactin secretion and synthesis. No change in reproductive organ weights was seen in treated animals. Hypoprolactinemia had no effect on plasma testosterone or androstenedione levels and testicular androstenedione content, but decreased significantly testicular testosterone content. These findings indicated that experimental hypoprolactinemia induced a decrease in testicular testosterone content without affecting androgens levels.     

The possible role of calmodulin in the inhibition of prolactin secretion by dopaminergic antagonists

Several previous reports have indicated that a number of dopaminergic antagonists paradoxically inhibit prolactin secretion at micromolar concentrations. It is well known that some of these drugs, including pimozide and the phenothiazines, are inhibitors of calmodulin activity. Here we report that micromolar concentrations of several dopaminergic antagonists inhibit prolactin secretion from isolated rat anterior pituitary cells and calmodulin activity (calmodulin-activated cyclic GMP phosphodiesterase). Inhibition of calmodulin activity may thus, at least partially, explain the inhibitory effect of these drugs on prolactin secretion.     

Stimulatory role for brain serotoninergic system on prolactin secretion in the male rat.

Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two times), a blocker of serotonin (5-HT) synthesis, considerably decreased brain 5-HT and plasma prolactin (PRL) levels in young male rats. Intraventricular (IVT) administration of 5,7-dihydroxytryptamine (5,7-DHT, 200 mug/20 mul), a neurotoxic drug which destroys 5-HT nerve terminals, induced, 3, 12, and 30 days after treatment, a marked depletion of brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and considerably reduced plasma PRL levels at each time interval. Feeding of rat for up to 4 days with a tryptophan (TP)-deficient diet, caused a depletion of brain 5-HT and 5-HIAA contents and did not modify plasma PRL levels. Addition of TP (2 g/kg of diet) to the TP-deficient diet resulted in increased brain 5-HT and 5-HIAA contents and significantly increased PRL levels. These data provide evidence for the role of the 5-HT system in the maintenance of tonic PRL secretion.     

Mechanism of the effect of urethane on the secretion of prolactin in the male rat

A subcutaneous injection of urethane (200 mg/100 g body wt.) into adult male rats resulted in a significant increase in serum prolactin (PRL) at 30 minutes. Subsequent measurements at 60, 90 and 120 minutes postinjection revealed a marked and rapid decrease in serum PRL to levels significantly lower than those of unanesthetized animals. The administration of the dopamine antagonist pimozide (8, 40 or 200 μg) 30 minutes after urethane injection elevated serum PRL levels in a dose-dependent manner and thus prevented the urethane-induced depression in serum PRL observed at 60 minutes postinjection. Hypothalamic synthesis of ¹⁴C-dopamine from its precursor ¹⁴C-tyrosine was measured in both urethane-anesthetized and unanesthetized rats. The synthesis of hypothalamic dopamine was dramatically increased in the urethane-anesthetized animals as compared to newly synthesized hypothalamic dopamine levels in the unanesthetized controls. These results indicate that the PRL-inhibitory effects of urethane anesthesia in the rat may be exerted through increased dopaminergic activity.