Capsaicin inhibits the pentagastrin-stimulated gastric acid secretion in anaesthetized rats with acute gastric fistula.

The effect of capsaicin on basal and pentagastrin-stimulated gastric acid secretion was investigated in the urethane anaesthetized acute gastric fistula rat. Gastric acid secretion was measured by flushing of the gastric lumen with saline every 15 min or by continuous gastric perfusion. Capsaicin given into the rat stomach at 120 ng x mL(-1) prior to pentagastrin (25 microg x kg(-1), iv) reduced gastric acid secretory response to pentagastrin by 24%. Intravenous (iv) capsaicin (0.5 microg x kg(-1)) did not reduce the pentagastrin-stimulated gastric acid secretion. After topical capsaicin desensitization (3 mg x mL(-1)), basal gastric acid secretion and that in response to pentagastrin (25 microg x kg(-1), intraperitonaeally) was unaltered compared with the control group. Data indicate that topical capsaicin inhibits gastric acid secretion stimulated with pentagastrin in anaesthetized rats.     

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.     

Effect of resiniferatoxin on stimulated gastric acid secretory responses in the rat

The effect of the capsaicin analogue ‘resiniferatoxin’ (RTX) was studied on basal and stimulated gastric acid secretory responses following sc bethanechol (1.5 mg/kg), sc pentagastrin (50 μg/kg) and sc histamine (0.5 and 2.5 mg/kg) in the 1-h pylorusligated plus saline (2 ml ig)-treated rats. Resiniferatoxin applied intragastrically in doses of 0.6 and 1 μg/kg at time of pylorus-ligation and administration of the above secretagogues reduced acid secretory respones to bethanechol by 18.3 and 26.4%, to 0.5 mg/kg histamine by 39.9 and 44.6%, to 2.5 mg/kg histamine by 21.3 and 40.8% and to pentagastrin by 10.2 and 30.9% respectively. A single sc injection of 0.4 μg/kg of RTX abolished basal secretion in pylorus ligated rats (which did not receive ig saline). Our results indicate that locally applied RTX is capable of inhibiting basal secretory responses and modifying gastric acid responses stimulated with histamine, bethanechol or pentagastrin in the rat.     

Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor

We previously reported the impaired HCO₃⁻ secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (N^G-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg/kg, ip) and used after 1, 3–4, and 5–6 weeks of diabetes with blood glucose levels of > 300 mg/dL. Under urethane anesthesia the HCO₃⁻ secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. L-NAME (20 mg/kg × 2) or insulin (4 units/rat) was administered sc for 4–5 weeks, starting 1 week after STZ treatment. The duodenal HCO₃⁻ secretory responses to various stimuli such as mucosal acidification (10 mM HCl for 10 min), 16,16-dimethyl prostaglandin E₂ (dmPGE₂: 10 μg/kg, iv), and vagal stimulation (0.5 mA, 2 ms, 3 Hz) were significantly decreased in STZ-treated rats, depending on the duration of diabetes. Repeated administration of L-NAME, starting from 1 week after STZ treatment, significantly reduced blood glucose levels toward normal values and restored the HCO₃⁻ responses to various stimuli in STZ rats, the effects being similar to those observed after supplementation of insulin. Diabetic rats developed duodenal lesions after perfusion of the duodenum with 150 mM HCl for 4 h, but this ulcerogenic response was significantly inhibited by the repeated treatment with L-NAME as well as insulin. We conclude that L-NAME is effective in ameliorating hyperglycemic conditions in STZ-diabetic rats, similar to insulin, and restores the impaired HCO₃⁻ secretion and the increased mucosal susceptibility to acid in diabetic rat duodenums.     

Effect of atrial peptide on gastric acid secretion in rats

The effect of synthetic rat atriopeptin (AP) II was examined on basal, vagally and carbachol-induced gastric acid secretion in anesthetized rats. AP II infusion, at stepwise increasing doses of 2, 20 and 100 ng/kg/min, had no effect on basal acid secretion. At doses of 2 and 20 ng/kg/min, AP II augmented vagally induced acid secretion significantly. The secretory response to vagal stimulation + AP II 20 ng/kg/min was completely abolished by atropine. In contrast a higher dose of AP II (50 ng/kg/h) reduced vagally induced acid secretion significantly. This dose of AP II also reduced acid secretion during direct cholinergic stimulation by carbachol, while the lower dose of 20 ng/kg/min had no effect on carbachol-induced acid secretion. The present data demonstrate for the first time an effect of atrial peptide on gastric acid secretion. At lower doses AP II augments the vagal influence on parietal cell function perhaps by augmenting vagally induced acetylcholine release. At higher doses AP II exerts an inhibitory effect on parietal cell function during vagally and carbachol-induced acid secretion, suggesting different and as yet unknown mechanisms of action. These results raise the possibility that the heart can exert a hormonally mediated influence on the regulation of gastric acid secretion.     

Multiple effects of phorbol ester on secretory activity in rabbit gastric glands and parietal cells

Acid secretory activity and respiration in rabbit gastric glands are stimulated by cAMP-dependent and -independent agonists. Potentiation between agonists suggests interaction of the activation pathways. Regulation of secretory response by protein kinase C was investigated with 12-0-tetradecanoyl phorbol-13-acetate (TPA). TPA elevated basal respiration, pepsin release, and acid secretion but inhibited histamine and carbachol stimulation of acid secretion by gastric glands, as measured by [dimethylamino-14C]aminopyrine accumulation. The inhibition of histamine response was specific for protein kinase C activators, occurred after a 20-min lag, and was not reversed by removal of TPA after 3 min of preincubation. TPA pretreatment inhibited acid secretory responses to cholera toxin and forskolin but enhanced the response to cAMP analogues. Cholera toxin and pertussis toxin simulated ADP-ribosylation of 45 and 41 kDa proteins, respectively, in parietal cell membranes. Therefore, both stimulatory (Gs) and inhibitory (Gi) GTP binding proteins of adenylyl cyclase appear to be present in parietal cells. Pretreatment with pertussis toxin attenuated PGE2 but not TPA inhibition of histamine stimulation of aminopyrine accumulation. Thus, the inhibitory effect of TPA does not appear to be associated with an action on Gi. The results with histamine and carbachol suggest that protein kinase C may regulate both cAMP-dependent and -independent stimulation of parietal cell acid secretion.     

Effects of a New Thyrotropin Releasing Hormone Analogue, YM-14673, on the In Vivo Release of Acetylcholine as Measured by Intracerebral Dialysis in Rats

The effects of a new thyrotropin releasing hormone (TRH) analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on the release of acetylcholine (ACh) in free-moving rats were examined in vivo by intracerebral dialysis. In the frontal cortex, YM-14673 (0.1-0.3 mg/kg) caused a significant dose-dependent increase in the extracellular levels of ACh, suggesting that YM-14673 stimulated the ACh release. These actions of YM-14673 were about 50 times more potent than those of TRH. On the other hand, extracellular levels of ACh in caudate nucleus were not changed following injection of YM-14673 even at 3 mg/kg. TRH and methamphetamine also increased the release of ACh in frontal cortex. Haloperidol prevented the increase in the methamphetamine-induced release of ACh, whereas the increased release of ACh produced by YM-14673 was partially antagonized by haloperidol. These results suggest that the dopaminergic system affects the facilitatory effects on the ACh release in the frontal cortex and that the stimulatory effect of YM-14673 on the frontal cholinergic neurons is partially mediated by dopaminergic neurons.     

Role of acetylcholine, histamine and gastrin in the acid response to intracisternal injection of TRH analog, RX 77368, in the rat

The role of gastrin, acetylcholine and histamine in the acid response to central vagal activation induced by intracisternal injection of the stable analog, RX 77368, was further investigated in urethane-anesthetized rats with gastric fistula. The gastrin monoclonal antibody 28-2 injected intravenously, at a dose previously shown to prevent gastrin-induced stimulation of acid secretion, did not alter the peak acid response to intracisternal injection of RX 77368 (15 ng). The TRH analog (30 ng) injected into the cisterna magna increased levels of histamine measured in the hepatic portal blood. Cimetidine administered at a dose which completely blocked the stimulation of gastric acid secretion produced by intravenous infusion of histamine, inhibited by 62% the stimulatory effect of intracisternal RX 77368 (30 ng). The M1 muscarinic antagonist, pirenzepine, completely prevented the acid secretion induced by intracisternal RX 77368 (30 ng). These results indicate that the acid response to central vagal activation by the TRH analog in rats involved M1 muscarinic receptors along with histamine release acting on H2 histaminergic receptors whereas gastrin does not appear to play an important role.     

Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats

Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 μg) inhibited dark-phase food intake, in a dose-dependent fashion, for >3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 μg) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 μg·kg(-1)·h(-1) iv), vagal stimulation with 2-deoxy-d-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin-stimulated gastric acid secretion, whereas 2-deoxy-d-glucose-stimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls (P < 0.01). Finally, nesfatin-induced Ca(2+) signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dose-dependent Ca(2+) increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca(2+) signaling in cultured DMNV neurons.     

Bombesin microinjected into the dorsal vagal complex inhibits vagally stimulated gastric acid secretion in the rat

Medullary sites of action for bombesin-induced inhibition of gastric acid secretion were investigated in urethane-anesthetized rats with gastric fistula. Unilateral microinjection of bombesin or vehicle into the dorsal vagal complex was performed using a glass micropipet and pressure ejection of 100 nl volume; gastric acid output was measured every 10 min by flushing the stomach. Microinjection of vehicle into the dorsal vagal complex did not alter gastric acid secretion (1.9 +/- mumol/10) from preinjection levels (2.9 +/- 0.8 mumol/10 min). Microinjection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, at a 77 pmol dose into the dorsal vagal complex stimulated gastric acid secretion for 100 min with a peak response at 40 min (24.1 +/- 3.2 mumol/10 min). Concomitant microinjection of RX 77368 (77 pmol) with bombesin (0.6-6.2 pmol) into the dorsal vagal complex dose dependently inhibited by 35-86% the gastric acid response to the TRH analog. Bombesin (6.2 pmol) microinjected into the dorsal vagal complex inhibited by 17% pentagastrin infusion-induced stimulation of gastric acid secretion (13.2 +/- 0.8 mumol/10 min) whereas intracisternal injection induced a 69% inhibition of the pentagastrin response. These results demonstrate that the dorsal motor complex is a sensitive site of action for bombesin-induced inhibition of vagally stimulated gastric secretion. However, other medullary sites must be involved in mediating the inhibitory effect of intracisternal bombesin on pentagastrin-stimulated gastric acid secretion.     

A comparative analysis of the effect of clofelin on gastric secretory function in man and dog

It is established that clofelin suppresses the human and dog insulin gastric secretion as well as human basal and histamine secretion. Clofelin has no effect on the secretory function of the dog stomach, stimulated by pentagastrin, carbachol histamine. It is supposed that clofelin-induced suppression of the human histamine gastric secretion takes place due to the inhibition of basal secretory component being a part of the common secretory effect on histamine. Clofelin may be promising drug in the treatment of patients with hypertension and duodenum ulcer.     

Reciprocal changes of plasma glucose and ketone bodies in fasted and acutely diabetic rats after CNS stimulation

To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ-diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats.     

Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat

We examined the role of prostaglandin E (EP) receptor subtypes in the regulation of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was superfused with saline, and the acid secretion was determined at pH 7.0 by adding 50 mM NaOH. The acid secretion was stimulated by intravenous infusion of histamine or pentagastrin. Various EP agonists were administered intravenously, whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min before EP agonists. PGE(2) suppressed the acid secretion stimulated by either histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect of PGE(2) was mimicked by sulprostone (EP(1)/EP(3) agonist) but not butaprost (EP(2) agonist) or AE1-329 (EP(4) agonist). The inhibitory effect of sulprostone, which was not affected by ONO-8711 (EP(1) antagonist), was more potent against pentagastrin- (50% inhibition dose: 3.6 mug/kg) than histamine-stimulated acid secretion (50% inhibition dose: 18.0 mug/kg). Pentagastrin increased the luminal release of histamine, and this response was also inhibited by sulprostone. On the other hand, AE1-329 (EP(4) agonist) stimulated the acid secretion in vagotomized animals with a significant increase in luminal histamine. This effect of AE1-329 was totally abolished by cimetidine as well as AE3-208 (EP(4) antagonist). These results suggest that PGE(2) has a dual effect on acid secretion: inhibition mediated by EP(3) receptors and stimulation through EP(4) receptors. The former effect may be brought about by suppression at both parietal and enterochromaffin-like cells, whereas the latter effect may be mediated by histamine released from enterochromaffin-like cells.     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg(-1) I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7-8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg(-1) urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 +/- 16.9 mg dl(-1), n = 6, prior to insulin and 42.0 +/- 8.4 mg dl(-1), n = 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg(-1), I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 +/- 14.0 mg dl(-1), n = 10, prior to insulin and 386.6 +/- 43.6 mg dl(-1), n = 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation.     

Development of gastric acid secretion in pigs from birth to thirty six days of age: the response to pentagastrin

The development of the gastric acid secretory response to pentagastrin was studied using 56 Large White x Landrace pigs, 0-36 days of age, 1.1-13.3 kg body-weight, obtained from 12 litters. Gastric acid secretory capacity was measured using a gastric perfusion technique and intravenous infusion of pentagastrin at dose rates of 2, 4 and 8 micrograms/h per kg. Significant positive linear correlations were found between stomach weight and age, and between stomach weight and body-weight during the 36 day period. The stomach weight to body-weight ratio increased for the first 3 days of age and then decreased during the following 33 days. Basal acid secretion was detected in all unsuckled pigs (n = 9), 2- to 8-h old. Maximal acid outputs in response to pentagastrin in these pigs were 0.16 +/- 0.02 mmol/kg body-weight and 0.034 +/- 0.001 mmol/g stomach weight. For the 56 pigs, significant linear correlations were found between maximal acid output and age, maximal acid output and body-weight, and maximal acid output and stomach weight. There was a significant linear increase in maximal acid output per unit stomach weight during the first 7 days of age, but during the subsequent 29 days the pattern of increase in gastric secretory capacity was slower and curvilinear. In the oldest nine pigs, 24-36 days of age, maximal acid outputs were 0.974 +/- 0.058 mmol/kg body-weight and 0.234 +/- 0.016 mmol/g stomach weight which represents a six to seven-fold increase compared with those determined in pigs at birth. Comparison of gastric acid secretory capacity determined under anaesthesia with that in conscious pigs showed that anaesthesia appeared to suppress basal output but had no effect on pentagastrin stimulated output. Comparison of response to histalog (betazole HCl) and pentagastrin indicated that newborn pigs were more sensitive to histalog but in pigs 9-38 days of age, there were no significant differences in responsiveness to the two secretagogues. These results show that gastric sensitivity to pentagastrin increases rapidly in the first week of life, that the stomach of the newborn pig is more sensitive to histalog than pentagastrin and that studies of the effect of pentagastrin on acid secretion, done under anaesthesia, are comparable to those in the conscious pig.     

Mechanisms underlying intracisternal TRH-induced stimulation of gastric acid secretion in rats

The neurohumoral pathways mediating intracisternal TRH-induced stimulation of gastric acid secretion were investigated. In urethane-anesthetized rats, with gastric and intrajugular cannulas, TRH or the analog [N-Val2]-TRH (1 microgram) injected intracisternally increased gastric acid output for 90 min. Serum gastrin levels were not elevated significantly. Under these conditions the TRH analog, unlike TRH, was devoid of thyrotropin-releasing activity as measured by serum TSH levels. In pylorus-ligated rats, gastrin values were not modified 2 h after peptide injection whereas gastric acid output was enhanced. TRH (0.1-1 micrograms) stimulated vagal efferent discharge, recorded from a multifiber preparation of the cervical vagus in urethane-anesthetized rats and the response was dose-dependent. The time course of vagal activation was well correlated with the time profile of gastric stimulation measured every 2 min. These results demonstrated that gastric acid secretory stimulation elicited by intracisternal TRH is not related to changes in circulating levels of gastrin or TSH but is mediated by the activation of efferent vagal pathways that stimulated parietal cell secretion.     

Sauvagine: effects on gastric acid secretion in rats

Intracerebroventricular (ICV) and subcutaneous (SC) injections of sauvagine powerfully inhibited gastric acid secretion stimulated by gastric distension and by 2-deoxy-D-glucose, but not by histamine in pylorus-ligated rats. Naloxone failed to antagonize the antisecretory effects of SC and ICV sauvagine. Intravenous infusion of sauvagine completely suppressed bethanechol-stimulated gastric secretion, significantly decreased pentagastrin-stimulated gastric secretion and did not modify histamine-stimulated gastric secretion in gastric-perfused rats. The inhibitory effect of sauvagine on gastric secretory response is not mediated through opioid or histamine receptors. It appears to be dependent on a vagal mechanism as well as other mechanisms that await further elucidation.     

Histamine dependence of pentagastrin-stimulated gastric acid secretion in rats.

Does gastrin stimulate gastric acid secretion by direct action on oxyntic cells, by releasing histamine, or by being potentiated by histamine? Previous studies in the mouse pointed to gastrin-regulated histamine release. Guinea pig and rat are well known to vary in their sensitivity to histamine. Therefore, the effects of histamine and pentagastrin were compared quantitatively on isolated, lumen-perfused, stomach preparations from these species in the absence and presence of histamine H2-receptor blockade. The loss of potency of histamine in the rat was mirrored by a loss of potency of pentagastrin consistent with the idea that pentagastrin acts by releasing histamine. In the rat, a well-defined pentagastrin curve was obtained in the presence of histamine H2-receptor block as though pentagastrin acts both directly on the oxyntic cell and indirectly by releasing histamine. It was not necessary to invoke a potentiating interaction between histamine and pentagastrin at the oxyntic cell; the two effects appeared simply to add. Potentiation was observed, however, between other combinations of stimuli, for example, between vagal nerve and pentagastrin stimulation. The physiological consequences of these results are discussed.     

Effects of vitamin E on microsomal Ca(2+) -ATPase activity and calcium levels in streptozotocin-induced diabetic rat kidney

Vitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca(2+)-ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca(2+)-ATPase activity and calcium levels in kidney of streptozotocin (STZ)-induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg x kg(-1) i.p.). After diabetes was verified, diabetic and age-matched control rats were untreated or treated with vitamin E (400-500 IU kg(-1) x day(-1), orally) for 10 weeks. Ca(2+)-ATPase activity and lipid peroxidation (MDA) were determined spectrophotometrically. Blood glucose levels increased approximately five-fold (> 500 mg x dl(-1)) in untreated-diabetic rats but decreased to 340+/-27 mg x dl(-1) in the vitamin E treated-diabetic group. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment markedly inhibited MDA levels in both control and diabetic animals. Ca(2+)-ATPase activity was 0.483+/-0.008 U l(-1) in the control group and significantly increased to 0.754+/-0.010 U l(-1) in the STZ-diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes-induced increase in Ca(2+)-ATPase activity (0.307+/-0.025 U l(-1), p < 0.001) and also reduced the enzyme activity in normal control rats. STZ-diabetes resulted in approximately two-fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes.     

Specific inhibition by ATP of histamine-stimulated acid secretion in the gastric glands of the rabbit]

The influence of adenosine 5'-triphosphate on gastric acid secretion stimulated by histamine, carbachol, dibutyryl-cAMP and the phosphodiesterase inhibitors 8-phenyl-theophylline and rolipram in isolated rabbit gastric glands was studied. Changes oi gastric acid secretion were measured by the aminopyrine accumulation method. Histamine-stimulated acid secretion was significantly inhibited by ATP 1 mM, whereas the secretory responses elicited by carbachol, dibutyryl-cAMP, 8-phenyl-theophylline or rolipram were not. Assays with indomethacin, a well known prostaglandin synthesis inhibitor, showed that this agent significantly reduced the inhibitory effect of ATP on histamine responses. The results indicate that the antisecretory effect of ATP was specific for histamine and that it was mediated, at least in part, via stimulation of endogenous prostaglandin production.