Cyclic nucleotide response to acid-secreting stimuli in guinea pig gastric mucosa in vitro
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To investigate the mechanism of intracellular transmission of three representative stimuli for gastric acid secretion, the dose-response relations of cyclic nucleotides accompanied by acid secretion stimulated by histamine, pentagastrin and bethanechol were comparatively studied using an in vitro preparation of guinea pig gastric mucosa surviving with a constant potential difference and acid secretion sensitive to amytal. The following results were obtained. (1) Both histamine-and pentagastrin-stimulated acid secretion accompanied a significant increase in cyclic AMP contents in the gastric mucosa and in the serosal solution without any increase in cyclic GMP. However, the ratio of the increase in acid secretion to that in cAMP content was signific antly greater with pentagastrin than with histamine, indicating that pentagastrin exerts its acid-secreting stimulus with less increase in cyclic AMP. (2) Stimulation with bethanechol resulted in a significant increase in the mucosal cyclic GMP content without any change in cyclic AMP. From these findings, it has been concluded that the above three stimuli are transmitted differently in the target cells, presenting evidence against the common final mediator theory of histamine for gastric acid sercetion.
Key Words:cyclic nucleotides gastric acid secretion in vitro histamine pentagastrin bethanechol
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- 2).Domschke W, Domschke S, Classen M, et al: Histamine and cyclic 3,5-AMP in gastric acid secretion. Nature 41: 454–455, 1973Google Scholar
- 11).Perrier CV, Laster L: Adenyl cyclase activity of guinea pig gastric mucosa; stimulation by histamine and prostaglandins. J Clin Invest 49: 73a, 1970Google Scholar
- 12).Levine RA, Washington A: Increased cyclic AMP production in human gastric juice in response to secretagogues. Gastroenterology 64: 863, 1973Google Scholar
- 16).Kuo J, Lee T, Reyes PL, et al: Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of guanosine 3′,5′-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem 237: 16–22, 1972Google Scholar
- 19).Kahlson G, Rosengren E: New approach to the physiology of histamine. Physiol Review 48: 155–196, 1968Google Scholar
- 20).Parsons ME: The antagonism of histamine H2-receptors in vitro and in vivo with particular reference to the actions of cimetidine. in “Cimetidine: Proceedings of the Second International Symposium on Histamine H2-Receptor Antagonists”, by Burland WL, Simkins MA, Excerpta Medica, Amsterdam-Oxford, 1977, p 13–20Google Scholar