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. 1988 Jan;395:319–331. doi: 10.1113/jphysiol.1988.sp016921

Investigation of mechanism of fade of gastrin-stimulated gastric acid secretion in the cat.

B H Hirst 1
PMCID: PMC1191996  PMID: 3411480

Abstract

1. In conscious cats prepared with gastric fistulae gastric acid secretion in response to pentagastrin was found to reach a maximum after 45 min of stimulation, and to fade thereafter. Over the period 45-150 min of stimulation the fade was 5.4-7.8% of the maximum response per 15 min. 2. Once the response to pentagastrin had declined, acid secretion could not be restored by doubling the dose of pentagastrin, although an equisecretory dose of histamine could restore it. 3. Low doses of histamine were additive to the pentagastrin acid secretory response; they tended to prolong the peak response, but did not alter the subsequent fade of acid secretion. The histamine H1-receptor antagonist mepyramine did not affect maximal acid secretion or the fade of the pentagastrin response. 4. The beta-adrenoreceptor antagonist propranolol increased the secretory response to pentagastrin, whilst the alpha-adrenoreceptor antagonist phentolamine was without effect. Neither agent altered the fade of the pentagastrin response. Isoprenaline tended to inhibit pentagastrin-stimulated acid secretion and increase the rate of fade of the response. 5. The 5-hydroxytryptamine (5-HT) receptor antagonist methylsergide slightly enhanced the acid secretory response to pentagastrin, but did not alter the fade of the response. A low dose of 5-HT did not alter pentagastrin-stimulated acid secretion, whilst a higher dose of 5-HT inhibited it. 6. Tetra-, penta- and pentadecagastrin demonstrated tachyphylaxis, i.e. progressively reduced responses upon repeated stimulation, whilst histamine did not. A low dose of histamine did not prevent tachyphylaxis of the pentagastrin response. 7. It is concluded that fade of pentagastrin-stimulated acid secretion in the conscious cat cannot be satisfactorily explained by the failure of the acid secretory mechanism, depletion of histamine, release of 5-HT, or activation of histamine H1-, alpha- or beta-adreno-, or 5-HT-receptors. The similar characteristics of fade and tachyphylaxis of gastrin-stimulated acid secretion are consistent with a common gastrin receptor inactivation or desensitization mechanism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albinus M., Blair E. L., Hirst B. H., Reed J. D., Schally A. V., Shaw B. The effects of somatostatin and metiamide on tachyphylaxis of pentagastrin stimulated gastric acid and pepsin secretion in the conscious cat. J Physiol. 1977 Apr;266(3):801–817. doi: 10.1113/jphysiol.1977.sp011794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bunce K. T., Parsons M. E., Rollings N. A. The effect of metiamide on acid secretion stimulated by gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate in the isolated whole stomach of the rat. Br J Pharmacol. 1976 Sep;58(1):149–156. doi: 10.1111/j.1476-5381.1976.tb07704.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Canfield S. P., Spencer J. E. The inhibitory effects of 5-hydroxytryptamine on gastric acid secretion by the rat isolated stomach. Br J Pharmacol. 1983 Jan;78(1):123–129. doi: 10.1111/j.1476-5381.1983.tb09371.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dinbar A., Grossman M. I. Interaction of stimulants of acid secretion in cat. Gastroenterology. 1972 Feb;62(2):242–246. [PubMed] [Google Scholar]
  5. Hirschowitz B. I., Sachs G. Restoration of homeostasis during histamine-stimulated gastric secretion by rapid intravenous injection of KCl. Gastroenterology. 1968 May;54(5):898–906. [PubMed] [Google Scholar]
  6. Hirst B. H., Labib L. A., Reed J. D. Characteristics and tachyphylaxis of gastrin-stimulated gastric acid secretion in the cat. J Physiol. 1978 Mar;276:1–11. doi: 10.1113/jphysiol.1978.sp012216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hirst B. H., Reed J. D., Lund P. K., Sanders D. J. Sensitivity of parietal cells to gastrin in the cat: comparison with man and dog. Digestion. 1980;20(5):300–306. doi: 10.1159/000198451. [DOI] [PubMed] [Google Scholar]
  8. Hirst B. H., Storey G. E., Venables C. W. Polytetrafluoroethylene (PTFE): a new material for the construction of gastrointestinal cannulae. Lab Anim. 1982 Jan;16(1):33–35. doi: 10.1258/002367782780908788. [DOI] [PubMed] [Google Scholar]
  9. Izzat A., Waton N. G. Release of 5-hydroxytryptamine by pentagastrin and its role in the 'fade' of stimulated gastric secretion in cats. J Physiol. 1987 Feb;383:499–507. doi: 10.1113/jphysiol.1987.sp016424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jaffe B. M., Kopen D. F., Lazan D. W. Endogenous serotonin in the control of gastric acid secretion. Surgery. 1977 Jul;82(1):156–163. [PubMed] [Google Scholar]
  11. Kasbekar D. K. Secretagogue-induced tachyphylaxis of gastric H + secretion and its reversal. Am J Physiol. 1972 Aug;223(2):294–299. doi: 10.1152/ajplegacy.1972.223.2.294. [DOI] [PubMed] [Google Scholar]
  12. Marsden C. D., Merton P. A., Morton H. B., Rothwell J. C., Traub M. M. Reliability and efficacy of the long-latency stretch reflex in the human thumb. J Physiol. 1981 Jul;316:47–60. doi: 10.1113/jphysiol.1981.sp013771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Reed J. D., Smy J. R. Effects of isopropylnoradrenaline on tachyphylaxis of gastrin stimulated gastric acid secretion and mucosal blood flow in the anaesthetized cat. J Physiol. 1976 Jan;254(1):153–168. doi: 10.1113/jphysiol.1976.sp011226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sanyal A. K., Waton N. G. Inhibition of gastric secretion by pentagastrin. J Physiol. 1972 Apr;222(1):47P–48P. [PubMed] [Google Scholar]
  15. Sanyal A. K., Waton N. G. The possible mechanism for the 'fade' in acid gastric secretion during continuous infusions of pentagastrin. J Physiol. 1976 Oct;261(2):445–451. doi: 10.1113/jphysiol.1976.sp011567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wan B. Y. Metiamide and stimulated acid secretion from the isolated non-distended and distended mouse stomach. J Physiol. 1977 Apr;266(2):327–346. doi: 10.1113/jphysiol.1977.sp011770. [DOI] [PMC free article] [PubMed] [Google Scholar]

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