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.     

Comparison of inhibitory effects of atropine, cimetidine, and atropine plus cimetidine on the indomethacin-provoked gastric mucosal erosions in rats

20 mg/kg-1 indomethacin suspended in 1% carboxymethyl-cellulose solution was given subcutaneously into rats to provoke gastric mucosal erosions during 5 h. Dose-dependent inhibitions of indomethacin erosions were observed following different doses of atropine (0.025; 0.2; 1.0 mg/kg-1) and cimetidine (2.5; 10; 50 mg/kg-1) administered intraperitoneally (25%; 38%; 81% and 0%; 42%; 89% respectively). More pronounced inhibitory effects have been obtained with the combinations of both drugs (51%; 68%; 92%). In particular there was a remarkable potentiated synergism in the lowest doses of atropine and cimetidine (51%, against 0% and 25%). These results provide further evidence of synergism of histamine H2-receptor blockers and anticholinergics, which combinations would be useful, for example, in peptic ulcer therapy.     

The effects of hexamethonium and atropine on gastric secretion elicited by histamine,pentagastrin and choline esters in the dog

The effects of hexamethonium and atropine were investigated on gastric secretion elicited by different secretory stimulants in the Heidenhain pouch dog. Hexamethonium inhibited secretion induced by bethanechol or carbachol, had no significant effect against histamine, and potentiated pentagastrin-induced secretion. Atropine inhibited secretion induced by bethanechol, carbachol and pentagastrin, but at similar dose levels was ineffective against histamine.     

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.     

Effect of cimetidine on pentagastrin- and meal-stimulated gastric acid secretion and serum gastrin before and after one month of daily cimetidine treatment

Conclusions Compared to the pretreatment studies, after 1 month of daily C: (1) 300 mg of oral C produced significantly less inhibition of peptone-stimulated gastric acid secretion (Table 1); (2) serum gastrin response to PM was significantly greater; and (3) the duration of the inhibitory effect of 300 mg of C i.v. on PG-stimulated gastric acid secretion was significantly shortened (Table 1).     

Prostaglandin E2 and gastric acid secretion in man

1. Extracts of human stomach homogenized in Krebs solution had more PGE(2)-like activity than tissue homogenized in acid/ethanol or in the presence of indomethacin, indicating that the tissue can synthesize PGE(2).2. The distribution and synthesis of PGE(2)-like substance in human stomach was determined by extracting frozen sections cut parallel to the mucosal surface. Peak levels usually occurred at a depth of 0-600 mum in the mucosa.3. Small amounts of a PGE(2)-like substance were present in basal gastric juice, and its concentration was usually even lower in secretion stimulated by pentagastrin or histamine.4. Submaximal acid secretion produced by I.V. infusion of pentagastrin generally fell slightly when indomethacin was administered rectally to inhibit PG synthesis.5. These experiments, together with the findings that orally administered PGE compounds do not inhibit human gastric acid secretion, seem to argue against a possible inhibitory role for PGE(2) in gastric acid secretion in man.6. If this is so, it would follow that gastric bleeding caused by aspirin-like drugs is not due to increased acid secretion. A hypothesis is presented that tissue damage following vasoconstriction and ischaemia, due to inhibition of PG synthesis in blood vessels, contributes to the bleeding.