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The effect of CCK B /gastrin antagonists on stimulated gastric acid secretion in the anaesthetized rat
Author(s) -
Hayward N.J.,
Harding M.,
Lloyd S.A.C.,
McKnight A.T.,
Hughes J.,
Woodruff G.N.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12535.x
Subject(s) - gastrin , secretion , gastric acid , endocrinology , medicine , chemistry , cholecystokinin , pharmacology , receptor
1 The urethane‐anaesthetized, vagotomised rat preparation was used to investigate the effects of the histamine H 2 ‐antagonist ranitidine, the proton pump inhibitor omeprazole and the CCK B /gastrin antagonists CI‐988, PD 136450 and L‐365,260 on pentagastrin‐, histamine‐ and bethanechol‐induced gastric acid secretion. 2 The novel CCK B /gastrin antagonists CI‐988 and PD 136450, and L‐365,260 dose‐dependently inhibited pentagastrin‐induced secretion. The ED 50 value for PD 136450 was 0.05 μmol kg −1 , the same following intravenous or subcutaneous administration. 3 CI‐988 and PD 136450 administered subcutaneously at dose levels highly effective for antagonism of pentagastrin responses had no effect on basal acid secretion. 4 Ranitidine inhibited pentagastrin‐, bethanechol‐, and histamine‐induced acid secretion, whereas the CCK B /gastrin antagonists inhibited only the secretory response to pentagastrin. 5 The selective CCK A antagonist, devazepide, was inactive at up to 300 μmol kg −1 i.p. against the three stimulants of acid secretion. 6 CI‐988 and PD 136450 will be useful research tools with which to investigate the role of CCK B /gastrin receptors in gastric acid secretion and the trophic activities of gastrin and cholecystokinin (CCK) on the gastrointestinal tract.