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

Hirst, Barry H.

doi:10.1113/jphysiol.1988.sp016921

Cited by 1 publication

(10 citation statements)

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“…The rate of fade of the pentagastrin response expressed as a percentage of the peak response was not related to the dose of pentagastrin, declining at about 36% 16min-. This value is considerably greater than values, 4.6-7.8% 15min'1, obtained for the decline of acid secretion in the anaesthetized and conscious cat and conscious rat (Reed & Smy, 1976;Albinus et al, 1977;Hirst et al, 1978;EmAs et al, 1981;Hirst, 1988). The fade of the response in vitro is unlikely to be explained by depletion of an essential nutrient.…”

Section: Mechanisms Offade and Tachyphylaxismentioning

confidence: 54%

“…Tachyphylaxis, the phenomenon of progressively reduced responses upon repeated stimulation by the same secretagogue, of pentagastrin-stimulated acid secretion has also been observed in the rat isolated stomach and gastric mucosa (Bunce et al, 1976;Main & Pearce, 1978). Fade and tachyphylaxis are common to all gastrin peptides (Hirst et al, 1978;Hirst, 1988). Studies in the cat in vivo have indicated that fade of the acid secretory response to gastrin may be related to release of an inhibitor (Izzat & Waton, 1987), a limiting gastric mucosal blood flow (Reed & Smy, 1976), and/or inactivation or desensitization of gastrin receptors (Albinus et al, 1977;Hirst et al, 1978;Hirst, 1988).…”

Section: Introductionmentioning

confidence: 93%

“…This effect has (Emas et al, 1981) as well as other mammalian species in vivo (e.g. Hirschowitz & Sachs, 1969;Hirst Present address: Norwich-Eaton Ltd, Newcastle upon et al, 1978;Hirst, 1988). Fade of the acid secretory Tyne.…”

Section: Introductionmentioning

confidence: 96%

“…Fade of the acid secretory Tyne. response is a particular feature of stimulation with Albinus et al, 1977;Hirst, 1988). The acid secretory response to pentagastrin in the rat in vitro, as well as in vivo, demonstrates fade (Main & Pearce, 1978;Boughton-Smith & Whittle, 1981).…”

Section: Introductionmentioning

confidence: 96%

“…Fade and tachyphylaxis are common to all gastrin peptides (Hirst et al, 1978;Hirst, 1988). Studies in the cat in vivo have indicated that fade of the acid secretory response to gastrin may be related to release of an inhibitor (Izzat & Waton, 1987), a limiting gastric mucosal blood flow (Reed & Smy, 1976), and/or inactivation or desensitization of gastrin receptors (Albinus et al, 1977;Hirst et al, 1978;Hirst, 1988). In the present experiments, we have characterized acid secretory responses to pentagastrin in vitro, in the absence of vascular and external neural influences, in the rat isolated gastric mucosa.…”

Section: Introductionmentioning

confidence: 99%

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Fade and tachyphylaxis of gastric acid secretory response to pentagastrin in rat isolated gastric mucosa

Hirst

Holland

Parsons³

et al. 1988

British J Pharmacology

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Gastric acid secretory responses to pentagastrin were characterized in the rat isolated gastric mucosa. In particular, the mechanisms underlying fade, declining response upon continued stimulation, and tachyphylaxis, progressively reduced responses upon repeated stimulation, were investigated. Pentagastrin, 10−9‐10−7m, resulted in concentration‐related increases in acid secretion, with a mean maximum of 2.65 μmolcm−2h−1 in response to pentagastrin, 10−7m. Higher concentrations of pentagastrin produced sub‐maximal secretory rates; we define this as auto‐inhibition. The responses to all concentrations of pentagastrin demonstrated fade. The rate of fade was correlated with the maximum acid secretory rate, declining at about 36% of the peak over the first 16min. The Po2, Pco2, [HCO3−], pH, [glucose], [lactate], [Na+] and [K+] did not decline during the fade of the acid secretory response to pentagastrin, 10−7 m. Addition of a second aliquot of pentagastrin was not able to reverse fade, but these tissues were responsive to histamine. Replacement of the serosal solution, before addition of a second aliquot of pentagastrin, increased the acid response from 3% to 24% of the first response. Serosal solution from donor tissues, allowed to respond to pentagastrin and then the acid secretion to fade, was able to stimulate secretion in fresh recipient tissues, although at lower rates. Acid secretory responses to a second dose of pentagastrin were not significantly different, whether the tissues were previously unstimulated, or stimulated with pentagastrin washed out after attaining its peak secretory response (after 10–20 min). The second response was significantly reduced if the first response was allowed to fade with the pentagastrin in contact for 100min; i.e. fade significantly influenced the extent of tachyphylaxis. Proglumide, 10−2m, a gastrin receptor antagonist, and omeprazole, 10−5 m, an inhibitor of the gastric (H+ + K+)‐ATPase, both inhibited pentagastrin‐stimulated acid secretion to similar extents. The second response to pentagastrin after pentagastrin alone, or pentagastrin plus omeprazole were both reduced compared to responses after no stimulation or omeprazole alone, respectively. After pentagastrin plus proglumide, the second response to pentagastrin was not lower than after proglumide alone. Proglumide, but not omeprazole, therefore, prevented pentagastrin tachyphylaxis. It is concluded that gastrin fade and tachyphylaxis are related phenomena. Part of the fade may be due to release of an inhibitor(s). The major proportion of tachyphylaxis is a result of specific interaction of gastrin with its receptors.

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