Intravenous Pentagastrin as a Partial Agonist of Gastric Secretion in Man: Evidence in Favor of the Existence of Hormonal Inhibitory Sites

Prugh, M.F.; Schorr, B.; Vlahčevič, Z. Reno; Makhlouf, Gabriel M.

doi:10.1016/s0016-5085(75)80047-3

Cited by 10 publications

(1 citation statement)

References 14 publications

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“…Sub-maximal acid secretory rates in response to large doses of gastrin have also been obtained in the dog and cat in vivo (Emas & Grossman, 1967;Hirst et al, 1978). It has been proposed that the auto-inhibition observed with high concentrations of gastrin is the result of an interaction with low-affinity inhibitory receptors (Ariens, 1964;Prugh et al, 1975;Davison & Najafi-Farashah, 1982). This postulated second receptor may not be localised to the parietal cell (Soll et al, 1984a).…”

Section: Acid Secretory Response To Pentagastrinmentioning

confidence: 99%

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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Section: Acid Secretory Response To Pentagastrinmentioning

confidence: 99%

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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Absence of Tachyphylaxis in Gastric Acid Secretion During Pentagastrin Infusion

Chin

MacLeod

Mahon

1986

The Journal of Clinical Pharma

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Tachyphylaxis to stimulation of gastric juice secretion during intravenous pentagastrin (PG) infusion has been reported in animal studies. We assessed the course of gastric response to PG 2 micrograms/kg/hr over eight hours in eight healthy subjects. Peak H+, pepsin, and volume secretions occurred during the second half hour of stimulation. Peak H+ output was 11.6 +/- 1.3 mmol/0.5 hr or 7.6 +/- 0.8% of the total eight-hour secretion. During subsequent half-hour collection intervals, there was no significant decline in response, and the average output was 10.3 +/- 0.4 mmol/0.5 hr (6.5 +/- 0.1%). Peak pepsin and volume secretions were respectively 10.0 +/- 1.4% (74.8 +/- 11.6 mg/0.5 hr) and 8.8 +/- 1.1% (146.3 +/- 17.4 mL/0.5 hr) of the total eight-hour secretion. Although there was a significant decline in pepsin and volume response subsequent to the peak output, the decline was not continuous, and pepsin and volume secretions were maintained, respectively, at 6.0 +/- 0.2% (46.1 +/- 2.5 mg/0.5 hr) and 6.2 +/- 0.1% (107.5 +/- 3.0 mL/0.5 hr) of the total eight-hour secretion. Our study did not demonstrate any tachyphylaxis in H+ response to continuous PG stimulation. This model appears to be a valid tool for the assessment of histamine-H2 antagonist effects on stimulated gastric juice secretion over 8 hours in humans.

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The effect and mechanism of the prokinetic action of cisapride on gastrointestinal smooth muscle

1993

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Cisapride is a new prokinetic agent which can facilitate or restore motility throughout the entire gastrointestinal tract. Although facilitation of acetylcholine release has been suggested, the mechanism of action of cisapride is not clear. To investigate the effect and mechanism of action of cisapride, we used isolated muscle strips (with mucosa and submucosa removed) of guinea pig antrum, ileum and colon to study: (1) the dose response to cisapride, (2) the effect of antagonists (atropine and tetrodotoxin) on the stimulatory effect of cisapride. Besides these studies, we also used 3H-acetylcholine release method to investigate the acetylcholine release effect of cisapride. Cisapride elicited a dose-related enhancement of baseline activity (motility index) on the antrum and contraction on the ileum and colon at the dose of 4, 40 and 400 nM. At higher doses (4 microM) cisapride caused inhibition. This bell-shaped dose response curve suggested that cisapride might be autoinhibitory or that the receptors of cisapride might consist of high affinity stimulatory and low affinity inhibitory sites. The stimulatory responses elicited by cisapride (400 nM) were not significantly inhibited by atropine and tetrodotoxin in the antrum, ileum and colon. This suggested that cisapride might act directly on the smooth muscle. Cisapride (400 nM) evoked a rather small increase of 3H-acetylcholine release on the antrum, ileum and colon. Because the percentage of increase was small and we had demonstrated that the stimulatory effects of cisapride were not blocked by atropine and tetrodotoxin, the acetylcholine release effect of cisapride was considered unimportant.

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Intravenous Pentagastrin as a Partial Agonist of Gastric Secretion in Man: Evidence in Favor of the Existence of Hormonal Inhibitory Sites

Cited by 10 publications

References 14 publications

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

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

Absence of Tachyphylaxis in Gastric Acid Secretion During Pentagastrin Infusion

The effect and mechanism of the prokinetic action of cisapride on gastrointestinal smooth muscle

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