The effects of somatostatin and metiamide on tachyphylaxis of pentagastrin stimulated gastric acid and pepsin secretion in the conscious cat.

1. Pentagastrin stimulated gastric acid and pepsin secretions show parallel rates of tachyphylaxis in the conscious cat. The responses to histamine show only slight tachyphylaxis. 2. Somatostatin 10 microng.kg(-1).hr(-1) inhibits pentagastrin but not histamine stimulated acid secretion and inhibits pentagastrin stimulated pepsin secretion. 3. The inhibition of pentagastrin stimulated acid and pepsin secretion by Somatostatin delays the tachyphylaxis of these responses, but the rates of tachyphylaxis when they do subsequently occur are identical. 4. Metiamide 10 mg-kg(-1)-hr(-1) equally inhibits histamine and pentagastrin stimulated acid secretion but does not inhibit pentagastrin stimulated pepsin secretion. 5. Inhibiton of acid secretion during metiamide infusion neither prevents nor delays acid nor pepsin tachyphylaxis. 6. It is suggested that tachyphylaxis of acid and pepsin secretion is a gastrin receptor phenomenon and that Somatostatin occupies or modifies the behaviour of these receptors, preventing tachyphylaxis. Metiamide, however, exerts its action only on the histmine H2-receptor and not the gastrin receptor mechanism, and this apparently does not prevent or delay acid tachyphylaxis.     

Effect of atropine and cimetidine combinations on pentagastrin stimulated maximal gastric acid secretion in man

Recently it has been reported that anticholinergics were able to increase the inhibitory effect on gastric secretion of specific histamine H2-receptor antagonists. The aim of the present study was to determine the degree of increased inhibition of gastric acid secretion and also to introduce an exact method for measuring the gastric acid output. Maximal gastric acid secretion provoked by continuous pentagastrin infusion 3.4-4.0 micrograms X kg-1 h-1) was dose-dependently inhibited by intravenous (i.v.) atropine (0.002; 0.003; 0.004 mg X kg-1) and cimetidine (1.0; 1.5; 2.0 mg X kg-1). A potentiated synergism was observed on the simultaneous administration of atropine and cimetidine, suggesting the good effect of a low dose combination of atropine and cimetidine in the therapy of peptic ulcer.     

The location of the chemoreceptor controlling gastric acid secretion during hypoglycaemia

1. The injection of 2-deoxy-D-glucose directly into the lateral hypothalamic area of rats, but not elsewhere, caused a prompt and sustained secretion of acid by the stomach at a rate comparable to that due to insulin hypoglycaemia.2. Acid secretion provoked by such injections, like that resulting from hypoglycaemia, could be stopped by raising the plasma glucose concentration by the intravenous infusion of glucose.3. Unilateral intrahypothalamic injection of 2-deoxy-D-glucose activated both vagi for, although cutting one vagus reduced the secretion, division of both was necessary to abolish it.4. Gastric acid secretion evoked by a systemic stimulus (insulin-induced hypoglycaemia or intravenous 3-O-methylglucose) could be prevented by inactivating the lateral hypothalamic area on each side with phenol or lignocaine.5. It is concluded that there exists in the lateral hypothalamic area a chemoreceptor, responsive to a lack of metabolizable glucose, which can initiate and sustain the vagally mediated secretion of acid by the stomach.     

The release of histamine during gastric acid secretion in conscious rats

1. Conscious gastric-cannulated rats were given [(3)H]histidine and aminoguanidine by dosage procedures intended to build up fast-turnover and slow-turnover pools of tissue [(3)H]histamine. Acid secretion was stimulated by I.V. infusion of pentagastrin, and the [(3)H]histamine content of gastric juice and excretion in urine were determined at 30 min intervals.2. The amount of [(3)H]histamine in gastric juice derived from either a slow-turnover or fast-turnover pool was very low in unstimulated animals, and was not altered during pentagastrin-stimulated acid secretion.3. From a slow-turnover pool pentagastrin caused increased urinary excretion of [(3)H]histamine. This was abolished by gastrectomy, so that the [(3)H]histamine liberated by pentagastrin from this pool appears to have been derived from the stomach. Evidence was not found for the existence of a slow-turnover histamine pool in the glandular mucosa of the stomach, and the source within the stomach of this pentagastrin-liberated histamine is thus uncertain.4. From a fast-turnover pool pentagastrin did not cause an increased urinary excretion of [(3)H]histamine. The amount of [(3)H]histamine excreted by gastrectomized rats was not different from that produced by gastric-cannulated animals. This suggests that a high proportion of urinary histamine derived from a fast-turnover pool was non-gastric in origin.5. Differences in the time scale of [(3)H]histamine release and acid secretion were not found. In some experiments the urinary output of [(3)H]histamine was prolonged beyond the end of pentagastrin administration and gastric acid secretion. However, the overall data do not suggest that urinary histamine output and gastric acid secretion take different time courses.     

Effect of His-Phe,a competitive inhibitor of histidine decarboxylase,on gastric acid secretion in chronic gastric fistula rats: Delay in acid secretion response to pentagastrin

The dipeptide His-Phe, earlier shown to inhibit mammalian histidine decarboxylase, was analysed concerning its effectin vivo on pentagastrin-induced gastric acid secretion. Chronic gastric fistula rats were used and the effectors in saline were given as continuous i.v. infusions while acid was collected from the fistula. Addition of petagastrin to the infusion solution resulted in an immediate increase in the acid output of the control runs. In the His-Phe experiments the dipeptide was introduced one hour before pentagastrin. A significant decrease in the acid output was obtained. This effect was optimal at a dose of about 6 mg/h and during the first few hours of the experiments. In spite of the continuous His-Phe infusion the acid secretion increased with time to the control values.These results are discussed in relation to preliminary observations on effects of -fluoromethyl histidine on gastric acid secretion and the effect of this and His-Phe on gastric histamine content and histidine decarboxylase activity.     

Chemical stimulatory mechanism in gastric secretion.

1. The serum gastrin level, gastric mucosal blood flow and acid secretion from the canine Heidenhain pouch have been measured in response to the introduction of bovine serum albumin, pepsin-digested albumin, an amino acid mixture, liver extract and mannitol used as control. 2. Distention of the Heidenhain pouch with mannitol or albumnin at pH 5-0 produced a similar pressure-related increase of acid secretion reaching a peak of only 10 percent of the maximal response to histamine. Pepsin-digested albumin was capable of producing larger acid outputs than undigested albumin.The highest acid output, attaining about 80 percent of the maximal response to histamine, was obtained with liver extract both before and after exhaustive dialysis to remove all the amino acids and short peptide fragments. An amino acid mixture containing all essential amino acids was also found to stimulate acid secretion but a lesser degree than liver extract. 3. This concluded that it is not the intact protein but the products of its digestion, the polypeptides and free amino acids, which are potent chemical stimulants of acid secretion from the oxyntic gland area. Since the serum gastrin level was not changed during acid secretion induced by peptic digests bathing the oxyntic gland area, the mechanism of chemical stimulation appears to be gastrin-independent. 4. The response to chemical stimulation by peptic digests can be greatly potentiated by combining this with distention of the oxyntic gland area. Topical application of xylocaine or atropine causes a marked decrease of Heidenhain pouch response to peptic digests, suggesting a possible neural reflex component in the mechanism of chemical stimulation of the oxyntic gland area. 5. When the pH of the liver extract in the Heidenhain pouch was gradually decreased in sequential order from 5-0 to 1-0, this resulted in a pH-related decrease in acid secretion and in the mucosal blood flow falling to the basal level at pH 1-0. Exogenous secretion given in graded doses from 0-5 to 8-0 u./kg. hr caused a small but dose-related inhibition of acid response to liver extract accompanied by a decrease of mucosal blood flow but without any significant change in the serum gastrin level. 6. The results indicate that the chemical stimulation of the oxyntic gland area by peptic digests is capable of inducing acid secretion by a local, gastrin-independent, partially neural reflex mechanism; sensitive to pH, pressure and secretin.     

Intracerebroventricular pentagastrin fails to affect feeding and acid secretion in the rat

The recent finding of immunoreactive gastrin in the pituitary and hypothalamus of the pig, cow and rat suggests that this peptide may have a physiologic function in the central nervous system. Because gastrin is an important regulator of gastric acid secretion, and may also affect food intake, we tested the hypothesis that direct intracerebroventricular injection of pentagastrin may also affect these variables. The results fail to support the hypothesis.