Effects of a Specific Gastrin Antagonist on Gastric Acid Secretion in Pouch Dogs

Bedi, B.S.; Gillespie, G; Gillespie, Iain

doi:10.1016/s0140-6736(67)92711-0

Cited by 28 publications

(5 citation statements)

References 2 publications

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“…The drug is more effective in preventing secretion than in is given before hormone appears to be considerably smaller than 50 x 104. CONCLUSION This study of the action of SC 15396 on gastrinstimulated gastric secretion of the anaesthetized rat agrees with the results reported in conscious dogs (Bedi et al, 1967) that the drug is capable of preventing or abolishing such secretion.…”

Section: Resultssupporting

confidence: 91%

“…When given intravenously to dogs in a dosage of 2.2 to 4.2 mg/kg, it promptly inhibited secretion already established by prior infusion or injection of gastrin II, confirming the results reported by Bedi et al (1967) who used doses of 0175 to 1.5 mg/kg body weight. Intravenous injection of 1 mg/kg SC 15396 in dogs also promptly depressed the response to a constant infusion of Peptavlon.…”

Section: Discussionsupporting

confidence: 85%

“…Macleod and Hill could not demonstrate a similar protective effect of innervation when the secretory stimulus was gastrin II. However, Davison et al(1967) and Bedi et al (1967), using much smaller doses of SC 15396, demonstrated the same effect in pouch dogs when the secretory stimulus was feeding, the major secretory stimulus under such conditions being endogenous gastrin. In Macleod and Hill's experiments, much higher drug-hormone molar ratios were achieved in the experiments using gastrin II than in those using histamine, and it is possible that the protective effect of innervation becomes swamped at these higher ratios.…”

Section: Discussionmentioning

confidence: 88%

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Effects of SC 15396 on gastric secretion. 3. The action in the rat.

Thomson¹,

Sircus²

1968

Gut

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 88%

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Effects of SC 15396 on gastric secretion. 3. The action in the rat.

Thomson¹,

Sircus²

1968

Gut

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“…They concluded that the compound is a specific inhibitor of gastrin-induced acid secretion. Working on vagally innervated and denervated Heidenhain-type pouches in dogs, Bedi, Gillespie & Gillespie (1967a) found about 50% inhibition of pentagastrininduced and about 70% inhibition of gastrin IL-induced acid secretion. By contrast, the single intravenous injection of 10 mg of the antigastrin had no effect on the plateau responses of the vagally innervated pouches to the continuous intravenous infusion of histamine; accordingly, these authors designate the inhibition as specific.…”

Section: Discussionmentioning

confidence: 99%

Mode of Action of a Gastric‐secretion Antagonist

Kahlson

Rosengren

Svensson

1968

British Journal of Pharmacology and Chemotherapy

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We embarked on the present study with the object of throwing light on the mode of action of gastrin. In this study a compound with specific antigastrin properties would seem to be useful. The actions of the pure natural peptides, gastrins I and II, in stimulating and inhibiting gastric acid secretion, as stimulants of pepsin and pancreatic secretion, and of gastric and small intestinal tone and motility, have been recorded by Tracy & Gregory (1964). Little is known of the mechanisms by which the gastrins display these numerous actions. As to the mode of action of gastrin in exciting acid secretion, pertinent facts have recently appeared. It was disclosed that injection of gastrin, as well as feeding, distension, and vagus stimulation, produced a striking and long lasting elevation of the histamine forming capacity (HFC) within the region of the parietal cells (Kahlson, Rosengren, Svahn & Thunberg, 1964;Kahlson, Rosengren & Thunberg, 1967). These authors further found that the mucosal histamine formed at high rates was sufficient to stimulate acid secretion, that additional histamine was formed only in the region containing parietal cells, that the elevation of HFC was not merely a concomitant of the process of secretion per se, and that the elevation of HFC occurred in all species studied.The authors believe that gastrin acts by evoking a mobilization of histamine and a concurrent acceleration of HFC, thus providing adequate amounts of histamine available for effective stimulation of acid secretion, so a specific antigastrin was expected to hinder the elevation of mucosal HFC without lowering the sensitivity of the parietal cells to histamine. The present experiments reveal that the newly synthesized compound antigastrin (Cook & Bianchi, 1967), 2-phenyl-2-(2-pyridyl)-thioacetamide (SC-15396) inhibits acid secretion not by interfering with the elevation of mucosal HFC induced by gastrin but by rendering the parietal cells less sensitive to histamine. The lack of specificity is shown further by the present finding that antigastrin reduces the secretory response of the peptic cells to stimulation by gastrin and histamine. METHODS AnimalsThe rats used weighed about 200 g, and belonged to two strains; a strain bred at this Institute for gastric secretory studies, and Sprague-Dawley rats for determination of histamine forming capacity (HFC) of the glandular part of the gastric mucosa. Urinary histamine was estimated in the latter strain.

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“…Gastrin antagonists as therapeutic agents may also be available in the near future. The A ntigastrin described by Bedi et al [3] is obvi ously not a specific Gastrin antagonist : it also inhibits gastric secretion stim ulated by histam ine and insulin [5]. W hether immunological investigations employing Gastrin antibodies [27,29] will have thera peutic consequences has not been established.…”

mentioning

confidence: 99%

Gastrin and its Significance

Claßen¹

1968

Digestion

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Effects of a Specific Gastrin Antagonist on Gastric Acid Secretion in Pouch Dogs

Cited by 28 publications

References 2 publications

Effects of SC 15396 on gastric secretion. 3. The action in the rat.

Effects of SC 15396 on gastric secretion. 3. The action in the rat.

Mode of Action of a Gastric‐secretion Antagonist

Gastrin and its Significance

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