Effect of pancreastatin on pancreatic endocrine function in the conscious rat

We have studied the effects of pancreastatin on insulin and glucagon secretions in vivo in the conscious rat. Rats were prepared with a gastric fistula and with both external jugular veins cannulated. We found that an i.v. infusion of pancreastatin (1 and 10 nmol/kg/h) inhibited the plasma insulin response and increased the plasma glucose response to the intragastric infusion of glucose in a dose-dependent manner. Furthermore, the infusion of pancreastatin increased the plasma glucagon response to the i.v. infusion of arginine in a dose-dependent manner, and it inhibited the plasma insulin response. However, such an infusion of pancreastatin had no effect on the basal plasma glucose level, nor did it have any effect on plasma insulin and glucagon concentrations. Thus, it is suggested that in the rat, the newly discovered pancreastatin is a regulator of islet cell function.     

Galanin and pancreastatin inhibit stimulated insulin secretion in the mouse: comparison of effects

The effects of the two intrapancreatic peptides galanin and pancreastatin on basal and stimulated insulin and glucagon secretion in the mouse were compared. It was found that at 2 min after intravenous injection of galanin or pancreastatin (4.0 nmol/kg), basal plasma glucagon and glucose levels were slightly elevated. Galanin was more potent than pancreastatin to elevate basal plasma glucagon levels: they increased from 60 +/- 15 to 145 +/- 19 pg/ml (p less than 0.01) after galanin compared to from 35 +/- 5 to 55 +/- 8 pg/ml (p less than 0.05) after pancreastatin. Plasma insulin levels were lowered by galanin (p less than 0.05), but not by pancreastatin. CCK-8 (6.3 nmol/kg) or terbutaline (3.6 mumol/kg) markedly increased the plasma insulin levels. Galanin (4.0 nmol/kg) completely abolished the insulin response to CCK-8 (p less than 0.001), but pancreastatin (4.0 nmol/kg) was without effect. Galanin inhibited the insulin response to terbutaline by approximately 60% (p less than 0.01), but pancreastatin inhibited the insulin response to terbutaline by approximately 35% only (p less than 0.05). CCK-8 and terbutaline did both elevate plasma glucagon levels by moderate potencies: neither pancreastatin nor galanin could affect these responses. Thus, in the mouse, galanin and pancreastatin both inhibit basal and stimulated insulin secretion, and stimulate basal glucagon secretion. Galanin is thereby more potent than pancreastatin. The study also showed that galanin potently inhibits insulin secretion stimulated by the octapeptide of cholecystokin and by the beta 2-adrenoceptor agonist terbutaline, and that pancreastatin inhibits terbutaline-induced insulin secretion.     

Homologous pancreastatin inhibits insulin secretion without affecting glucagon and somatostatin release in the perfused rat pancreas.

The identification of pancreastatin in pancreatic extracts prompted the investigation of its effects on islet cell function. However, in most of the investigations to date, pig pancreastatin was tested in heterologous species. Since there is great interspecies variability in the amino acid sequence of pancreastatin, we have investigated the influence of rat pancreastatin on insulin, glucagon and somatostatin secretion in a homologous animal model, namely the perfused rat pancreas. During 5.5 mM glucose infusion, pancreastatin (40 nM) inhibited insulin secretion (ca. 40%, P less than 0.025) as well as the insulin responses to 10 mM arginine (ca. 50%, P less than 0.025) and to 1 nM vasoactive intestinal polypeptide (ca. 50%; P less than 0.05). Pancreastatin failed to significantly modify glucagon or somatostatin release under any of the above experimental conditions. In addition, a lower pancreastatin concentration (15.7 nM) markedly suppressed the insulin release evoked by 11 mM glucose (ca. 85%, P less than 0.05). Our present observations reinforce the concept that pancreastatin is an effective inhibitor of insulin secretion, influencing the B-cell function directly and not through an A-cell or D-cell paracrine effect.     

Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.     

Carbohydrates modulate opiate receptor mediated mechanisms during postprandial endocrine function

The present study was designed to determine the role of carbohydrates during naloxone-induced opiate receptor blockade upon the postprandial rise of plasma somatostatin (SLI), insulin and pancreatic polypeptide (PP) levels in response to protein and fat test meals in conscious dogs. Test meals consisting of 50 g liver extract + 50 g sucrose or 50 g corn oil + 50 g sucrose dissolved in 300 ml water were instilled intragastrically, respectively. Additionally, liver extract and fat meals were given with a concomitant intravenous infusion of glucose. To all test meals either naloxone (4 mg) or saline was added. The addition of sucrose to liver extract or the infusion of i.v. glucose during the liver meal abolished the inhibitory effect of naloxone on the rise of postprandial somatostatin levels which has been described recently. The addition of carbohydrate either orally or intravenously to the fat meal resulted in an even stimulatory effect of naloxone upon the rise of postprandial somatostatin levels. Insulin levels were not changed during liver extract + sucrose or i.v. glucose, respectively. When sucrose or i.v. glucose was administered together with the fat meal the addition of naloxone augmented postprandial insulin secretion. Pancreatic polypeptide (PP) release was augmented during the combination of sucrose or i.v. glucose with the fat and liver meal when naloxone was present in the meals. The present data demonstrate that the addition of carbohydrates either orally or intravenously to fat and protein meals modulates the effect of endogenous opiates in the regulation of postprandial somatostatin, insulin and pancreatic polypeptide release in dogs in a way that carbohydrates induce inhibitory mechanisms that are mediated via endogenous opiate receptors.     

Effect of neuropeptide Y on the hypothalamic-pituitary-adrenal axis in the dog

There is increasing evidence that neuropeptide Y (NPY) affects the release of pituitary hormones, including adrenocorticotropic hormone (ACTH). The present study was designed to clarify the mechanism by which NPY activates the hypothalamic-pituitary-adrenal (HPA) axis in the dog. Mongrel dogs were equipped with a chronic cannula allowing intra-third (i.t.v.) or intra-lateral (i.l.v.) cerebroventricular administration. A 1.19 nmol, i.t.v. dose of NPY produced as great an ACTH and cortisol response as did equimolar ovine corticotropin releasing factor (CRF). This action of NPY was dose-dependent and shared by peptide YY (PYY) and pancreatic polypeptide (PP), other members of the PP family peptide. Intravenously (i.v.) administered NPY (1.19-11.9 nmol) was much less potent than i.v. CRF in stimulating ACTH and cortisol secretion. However, i.v. NPY significantly increased plasma ACTH and cortisol concentrations, raising the possibility that NPY may modulate the activity of corticotrophs. We have next investigated the possible relationship between NPY and CRF on the HPA axis. Pretreatment with a novel CRF antagonist, alpha-helical CRF9-41 (130.9 nmol i.t.v. or 261.8 nmol i.v.), partly but significantly attenuated the ACTH and cortisol responses to i.t.v. NPY (1.19 nmol). Furthermore, adding a subthreshold dose of i.t.v. NPY (0.119 nmol) to i.t.v. CRF (1.19 nmol) or i.v. NPY (2.38 nmol) to i.v. CRF (0.595 nmol) resulted in the potentiation of CRF-induced ACTH secretion. These results indicate that NPY may activate the HPA axis in concert with CRF probably at hypothalamic and/or pituitary levels. The present findings that NPY evokes ACTH secretion and potentiates the effectiveness of CRF as a secretagogue, together with high concentrations of NPY in the hypothalamus and pituitary portal blood, suggest that NPY is involved in the multihormonal control of ACTH release.     

Effects of pancreastatin on insulin, glucagon and somatostatin secretion by the perfused rat pancreas

Pancreastatin is a novel peptide, isolated from porcine pancreatic extracts, which has been shown to inhibit glucose-induced insulin release "in vitro". To achieve further insight into the influence of pancreastatin on pancreatic hormone secretion, we have studied the effects of this peptide on unstimulated insulin, glucagon and somatostatin output, as well as on the responses of these hormones to glucose and to tolbutamide in the perfused rat pancreas. Pancreastatin strongly inhibited unstimulated insulin release as well as the insulin responses to glucose and to tolbutamide. It did not significantly affect glucagon or somatostatin output under any of the above-mentioned conditions. These findings suggest that pancreastatin inhibits B-cell secretory activity directly, and not through an A-cell or D-cell paracrine effect.     

Central action of insulin regulates pulsatile luteinizing hormone secretion in the diabetic sheep model

This study tested the hypothesis that central mechanisms regulating luteinizing hormone (LH) secretion are responsive to insulin. Our approach was to infuse insulin into the lateral ventricle of six streptozotocin-induced diabetic sheep in an amount that is normally present in the CSF when LH secretion is maintained by peripheral insulin administration. In the first experiment, we monitored cerebrospinal fluid (CSF) insulin concentrations every 3-5 h in four diabetic sheep given insulin by peripheral injection (30 IU). The insulin concentration in the CSF was increased after insulin injection, and there was a positive relationship between CSF and plasma concentrations of insulin (r = 0.80, P < 0.01). In the second experiment, peripheral insulin administration was discontinued, and the sheep received either an intracerebroventricular (i.c.v.) infusion of insulin (12 mU/day in 2.4 ml saline) or saline (2.4 ml/day) for 5 days (n = 6) in a crossover design. The dose of insulin (i.c.v.) was calculated to approximate the increase in CSF insulin concentration found after peripheral insulin treatment. To monitor LH secretory patterns, blood samples were collected by jugular venipuncture at 10-min intervals for 4 h on the day before and 5 days after the start of i.c.v. insulin infusion. To monitor the increase in CSF insulin concentrations, a single CSF sample was collected one and four days after the start of the central infusion. The i.c.v. insulin infusion increased CSF insulin concentrations above those in saline-treated animals (P < 0.05) and maintained them at or above the peak levels achieved after peripheral insulin treatment. Central insulin infusion did not affect peripheral (plasma) insulin or glucose concentrations. LH pulse frequency in insulin-treated animals was greater than that in saline-treated animals (3.5 +/- 0.2 vs. 2.3 +/- 0.3 pulses/4 h, P < 0.01), but it was less than that during peripheral insulin treatment (4.8 +/- 0.2 pulses/4 h, P < 0.01). Our findings suggest that physiologic levels of central insulin supplementation are able to increase pulsatile LH secretion in diabetic sheep with low peripheral insulin. These results are consistent with the notion that central insulin plays a role in regulating pulsatile GnRH secretion.     

Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats

We previously reported the stimulatory effect of endogenous nitric oxide (NO) on gastric acid secretion in the isolated mouse whole stomach and histamine release from gastric histamine-containing cells. In the present study, we investigated the effects of endogenous and exogenous NO on gastric acid secretion in urethane-anesthetized rats. Acid secretion was studied in gastric-cannulated rats stimulated with several secretagogues under urethane anesthesia. The acid secretory response to the muscarinic receptor agonist bethanechol (2 mg/kg, s.c.), the cholecystokinin(2) receptor agonist pentagastrin (20 microg/kg, s.c.) or the centrally acting secretagogue 2-deoxy-D-glucose (200 mg/kg, i.v.) was dose-dependently inhibited by the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 or 50 mg/kg, i.v.). This inhibitory effect of L-NNA was reversed by a substrate of NO synthase, L-arginine (200 mg/kg, i.v.), but not by D-arginine. The histamine H(2) receptor antagonist famotidine (1 mg/kg, i.v.) completely inhibited the acid secretory response to bethanechol, pentagastrin or 2-deoxy-D-glucose, showing that all of these secretagogues induced gastric acid secretion mainly through histamine release from gastric enterochromaffin-like cells (ECL cells). On the other hand, histamine (10 mg/kg, s.c.)-induced gastric acid secretion was not inhibited by pretreatment with L-NNA. The NO donor sodium nitroprusside (0.3-3 mg/kg, i.v.) also dose-dependently induced an increase in acid secretion. The sodium nitroprusside-induced gastric acid secretion was significantly inhibited by famotidine or by the soluble guanylate cyclase inhibitor methylene blue (50 mg/kg, i.v.). These results suggest that NO is involved in the gastric acid secretion mediated by histamine release from gastric ECL cells.     

Interaction between phosphoinositide turnover system and cyclic AMP pathway for the secretion of pancreastatin and somatostatin from QGP-1N cells.

It is found that secretion of pancreastatin and somatostatin from QGP-1N cells is regulated through muscarinic receptor-mediated activation of phosphatidylinositide hydrolysis system. In this report, whether the cAMP pathway interacts with the phosphoinositide turnover system for the secretion of pancreastatin and somatostatin from QGP-1N cells through muscarinic receptors was studied. Stimulation of QGP-1N cells with carbachol increased intracellular cAMP levels. The carbachol-induced increase in cAMP levels was inhibited by atropine. Calcium ionophore (A23187) and phorbol 12-myristate 13-acetate increased cAMP synthesis. Dibutyryl cAMP, forskolin and theophylline stimulated secretion of pancreastatin and somatostatin. When either dibutyryl cAMP, forskolin or theophylline was added in culture medium with A23187, phorbol ester or carbachol, a synergistic effect was found on pancreastatin and somatostatin secretion. These results suggest that interaction between the phosphoinositide turnover system and the cAMP pathway occurs in QGP-1N cells through muscarinic receptor stimulation for the secretion of pancreastatin and somatostatin.     

Effects of pancreastatin and chromogranin A on insulin release stimulated by various insulinotropic agents

The effects of porcine pancreastatin on insulin release stimulated by insulinotropic agents, glucagon, cholecystokinin-octapeptide (CCK-8), gastric inhibitory polypeptide (GIP) and L-arginine, were compared to those of bovine chromogranin A (CGA) using the isolated perfused rat pancreas. Pancreastatin significantly potentiated glucagon-stimulated insulin release (first phase: 12.5 +/- 0.9 ng/8 min; second phase: 34.5 +/- 1.6 ng/25 min in controls; 16.5 +/- 1.1 ng/8 min and 44.0 +/- 2.2 ng/25 min in pancreastatin group), whereas CGA was ineffective. The first phase of L-arginine-stimulated insulin release was also potentiated by pancreastatin (6.9 +/- 0.5 ng/5 min in controls, 8.4 +/- 0.6 ng/5 min in pancreastatin group), but not by CGA. Pancreastatin did not affect CCK-8 or GIP-stimulated insulin release. Similarly, CGA did not affect insulin release stimulated by CCK-8 or GIP. These findings suggest that pancreastatin stimulates insulin release in the presence of glucagon. Because pancreastatin can have multiple effects on insulin release, which are dependent upon the local concentration of insulin effectors, pancreastatin may participate in the fine tuning of insulin release from B cells.     

Pancreastatin distribution and plasma levels in the pig

Pancreastatin is a peptide isolated from porcine pancreas which has insulin-suppressive actions in vitro and sequence homology with chromogranin A. Using radioimmunoassay and immunocytochemistry we investigated whether pancreastatin has a more widespread distribution and a possible endocrine role in the pig. Pancreastatin immunoreactivity was found in plasma, adrenal gland, pancreas, anterior pituitary and throughout the gastrointestinal tract. The immunoreactivity was colocalized with chromogranin immunoreactivity in endocrine cells and ultrastructurally (in the pancreas) to storage granules. Characterization of pancreastatin-like immunoreactivity, using gel permeation and high performance liquid chromatography, separated 3 different pancreastatin-like immunoreactive forms: one molecular form, indistinguishable from synthetic pancreastatin 1-49, was predominant in pancreas and thyroid and released into the circulation postprandially. However, a high dose (greater than 1 nmol/l) infusion of pancreastatin 33-49 (the biologically active moiety in vitro) into conscious pigs had no effect on either basal or glucose-stimulated insulin secretion.     

Biological actions of peptide YY: effects on endocrine pancreas, pituitary-adrenal axis, and plasma catecholamine concentrations in the dog

The present study was designed to gather information on the biological activity of peptide YY (PYY) in conscious dogs. PYY was infused intravenously at a dose of 238 pmol/kg X h, and plasma concentrations of glucose, insulin, pancreatic polypeptide (PP), ACTH, cortisol and catecholamines (norepinephrine-NE; epinephrine-E; dopamine-DA) were subsequently measured. PYY significantly increased plasma insulin levels transiently without effect on plasma glucose, but decreased plasma PP levels during all infusion periods. PYY stimulated both plasma ACTH and cortisol secretion, and this action of PYY was also shared by PP, with PP being less potent in ACTH-cortisol release. PYY further elicited specific changes in plasma catecholamine concentrations, i.e. an increase of NE but not of E, which were in contrast to the effects of insulin-induced hypoglycemia. PP failed to alter plasma insulin and catecholamine concentrations. These results suggest that PYY can affect anterior pituitary hormone secretion, sympathetic nervous outflow and pancreatic endocrine activity in addition to its known actions on gastric and pancreatic secretion in the dog.     

Regulation of gastrointestinal function by multiple opioid receptors

Agonist and antagonist drugs possessing selectivity for individual types of opioid receptors have been employed in vitro and in vivo to determine the mechanisms by which opioids regulate gastrointestinal functions. Selective mu opioid agonists given by intracerebroventricular (i.c.v.) injection, by intrathecal (i.t.) injection, or by peripheral (s.c. or i.v.) injection in rats or mice decreased gastrointestinal transit and motility, inhibited gastric secretion, and suppressed experimentally-induced diarrhea. Selective delta agonists, by contrast, inhibited gastrointestinal transit after i.t., but not after i.c.v. or s.c. administration. Delta agonists also did not alter gastric secretion after i.c.v. or s.c. injection. However, delta agonists exhibited antidiarrheal effects after i.c.v., i.t., or s.c. administration. Kappa agonists given i.c.v. had no effect on gastrointestinal transit in rats or mice or on gastric secretion in rats, but exhibited antidiarrheal effects in mice. The kappa agonist U-50, 488H given peripherally increased gastric acid secretion. Different types of opioid receptors in different anatomical sites influence differently gastrointestinal motility and propulsion, gastric secretion, and mucosal transport. Brain, spinal cord, enteric neural and smooth muscle opioid receptors represent chemosensitive sites for regulation of gastrointestinal function.     

Inhibitory effect of pancreastatin on pancreatic exocrine secretion in the conscious rat

The effect of newly discovered pancreastatin on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine was examined in the conscious rat. Exogenous pancreastatin infusion (20, 100 and 200 pmol/kg.h) inhibited pancreatic protein and fluid outputs during BPJ diversion in a dose-dependent manner. Pancreastatin did not affect plasma cholecystokinin (CCK) concentrations. Pancreastatin (100 pmol/kg.h) inhibited CCK-stimulated pancreatic secretion, but did not inhibit secretin-stimulated pancreatic secretion. Pancreastatin alone, however, did not affect basal pancreatic secretion. In contrast, pancreastatin (10(-10)-10(-7)M) did not suppress CCK-stimulated amylase release from isolated rat pancreatic acini. These results indicate that pancreastatin has an inhibitory action on exocrine function of the pancreas. This action may not be mediated by direct mechanisms and nor via an inhibition of CCK release. It is suggested that pancreastatin may play a role in the regulation of the intestinal phase of exocrine pancreatic secretion.     

Impact of euglycaemia and hyperglycaemia on the release of growth hormone and prolactin in type II-diabetics

The influence of different blood glucose concentrations on the arginine (30 g/30 min i.v.) and TRH (400 micrograms i.v.) induced release of growth hormone and prolactin was studied in six male type II-diabetic patients. Blood glucose concentrations were clamped at euglycaemic (4-5 mmol/l) or hyperglycaemic (12-18 mmol/l) levels by means of an automated glucose-controlled insulin infusion system. The response of growth hormone to arginine, and irregular spikes in growth hormone concentrations following TRH seen in the euglycaemic state were suppressed during hyperglycaemia. The suppression of the arginine-induced release of growth hormone by hyperglycaemia was observed both with and without concomitant administration of exogenous insulin. The rise in serum prolactin concentrations in response to arginine was unaffected by hyperglycaemia, whereas the TRH-induced release of prolactin was suppressed. Since arginine induces the release of growth hormone and prolactin via the hypothalamus, while TRH acts at the pituitary level, the glycaemic state appears to exert a modulatory effect on the secretion of growth hormone and prolactin in type II-diabetics at both locations.     

Glucagon increases insulin levels by stimulating insulin secretion without effect on insulin clearance in mice

Circulating insulin is dependent on a balance between insulin appearance through secretion and insulin clearance. However, to what extent changes in insulin clearance contribute to the increased insulin levels after glucagon administration is not known. This study therefore assessed and quantified any potential effect of glucagon on insulin kinetics in mice. Prehepatic insulin secretion in mice was first estimated following glucose (0.35 g/kg i.v.) and following glucose plus glucagon (10 μg/kg i.v.) using deconvolution of plasma C-peptide concentrations. Plasma concentrations of glucose, insulin, and glucagon were then measured simultaneously in individual mice following glucose alone or glucose plus glucagon (pre dose and at 1, 5, 10, 20 min post). Using the previously determined insulin secretion profiles and the insulin concentration-time measurements, a population modeling analysis was applied to estimate the one-compartment kinetics of insulin disposition with and without glucagon. Glucagon with glucose significantly enhanced prehepatic insulin secretion (Cmax and AUC_0-20) compared to that with glucose alone (p < 0.0001). From the modeling analysis, the population mean and between-animal SD of insulin clearance was 6.4 ± 0.34 mL/min for glucose alone and 5.8 ± 1.5 mL/min for glucagon plus glucose, with no significant effect of glucagon on mean insulin clearance. Therefore, we conclude that the enhancement of circulating insulin after glucagon administration is solely due to stimulated insulin secretion.     

Effects of intraventricular administration of vasoactive intestinal peptide and neurotensin on salivary secretion and blood pressure in the rat

Studies were carried out to investigate central actions of vasoactive intestinal polypeptide (VIP) and neurotensin (NT) on systemic blood pressure (BP), heart rate (HR) and salivary secretion in urethane-anesthetized male rats. Intraventricular (i.c.v.) administration of VIP caused dose-related increases in BP, HR and salivary secretion. Nearly maximum values were obtained at the dose of 2.0 micrograms for BP and 10.0 micrograms for salivary secretion, whereas the increase in HR did not attain the maximum even with the dose of 10.0 micrograms. Administration of hexamethonium (i.v.) completely blocked the increasing response of BP and HR, and the administration of pimozide (i.p.) or phenoxybenzamine (i.v.) reduced them. The increasing response of salivary secretion was almost completely blocked by all of the drugs. The administration of NT (i.c.v.) produced no change in the BP, HR and salivary secretion. The present results indicate that, 1) centrally administered VIP may somehow augment the sympathetic nerve discharge and/or adrenal medulla secretion, and 2) central VIP may play a role in the control of salivary regulation, probably through sympathetic nerves.     

Stimulation of gastric acid secretion by progesterone metabolites as neuroactive steroids in anesthetized rats.

The effect of neuroactive progesterone metabolites, 5alpha- and 5beta-pregnan-3alpha-ol-20-one, and their stereoisomers at the 3 C site, 5alpha- and 5beta-pregnan-3beta-ol-20-one, on gastric acid secretion was investigated in urethane-anesthetized rats. Both 5alpha- and 5beta-pregnan-3alpha-ol-20-one dose-dependently (0.3-3 mg x kg(-1), i.v.) stimulated gastric acid secretion with an early onset of action. Their potency and efficacy were almost the equivalent of one another. In contrast, their stereoisomers did not have a significant effect even at 10 mg x kg(-1) (i.v.). The 5beta-pregnan-3alpha-ol-20-one (3 mg x kg(-1), i.v.)-stimulated gastric acid secretion was remarkably inhibited by bilateral vagotomy or pretreatment with atropine (1 mg x kg(-1), i.v.). An antagonist of the GABA(A) receptor, picrotoxin, at 3 and 6 mg x kg(-1) (i.v.), significantly inhibited the 5beta-pregnan-3alpha-ol-20-one (3 mg x kg(-1), i.v.)-stimulated gastric acid secretion. These results indicate that naturally occurring neuroactive steroids, 5alpha- and 5beta-pregnan-3alpha-ol-20-one, stimulate gastric acid secretion in a stereoselective and dose-dependent manner in urethane-anesthetized rats. It is likely that the action of these neuroactive steroids is of central origin and that interaction with GABA(A) receptors and stimulation of vagal pathway are involved in its mechanism of action.     

Effects of amino-acids on pancreatic hormones and gut glucagon-like immunoreactivity in the goose

In the goose, alanine and arginine, intravenously or orally administered, act in the same way on pancreatic hormones; they both stimulate insulin and glucagon secretions. Conversely, whereas alanine treatment has no effect on plasma gut GLI, oral arginine stimulates gut GLI secretion. Since stimulation of gut GLI secretion does not occur with i.v. arginine, it may be assumed that this secretion depends on the intestinal transit of arginine and, as already described (Sitbon and Mialhe 1979), of glucose. The results, compared with studies on a similar species (duck) and on mammals, point out that i.v. infusion of alanine stimulates IRI and GLI secretions in the goose and not in the duck. In the same way, arginine i.v. infusion, contrarily to the observation made in the duck, is without effect on gut GLI secretion in the goose. Furthermore, insulin seems to be able to inhibit the alpha cell response to arginine infusion, as in mammals, whereas this is not the case in ducks.