THE GASTRIC ANTISECRETORY ACTIONS OF PROSTAGLANDIN E₂ AND STABLE PROSTACYCLIN ANALOGUES AGAINST DIFFERENT SECRETAGOGUES IN PERFUSED WHOLE‐STOMACHS OF RAT OR MOUSE in vitro

Abstract

1 The characteristics of the antisecretory actions of prostaglandin E2 (PGE2) and two stable prostacycin analogues during different rates of acid stimulation have been evaluated in the lumen-perfused isolated whole stomach of the rat and mouse. 2 In the rat isolated stomach, histamine induced a dose-dependent increase in acid output. Preincubation with PGE2 caused a dose-related and surmountable inhibition. 3 The stable prostacycin analogues, 6/3-PGI1 and a 16-phenoxy derivative likewise caused a surmountable inhibition of histamine-stimulated acid output from rat stomach. 4 PGE2 had inconsistent actions on the acid secretion stimulated by pentagastrin, methacholine or dibutyryl cyclic adenosine 3',5'-monophosphate. 5 In the mouse isolated stomach, acid secretion was stimulated by low concentrations of histamine, pentagastrin or methacholine. 6 PGE2 failed to inhibit histamine-stimulated acid output from mouse stomach, but high concentrations of the potent 16-phenoxy analogue did show anti-secretory activity. 7 The results indicate the usefulness of the rat isolated stomach for studying the interaction of prostaglandins with the acid secretory process in mammalian gastric mucosa.

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

“…Moreover, after fade of the pentagastrin response was complete, histamine could still stimulate acid secretion at rates not different from those initially observed to pentagastrin, as has been previously demonstrated for frog isolated gastric mucosa (Kasbekar et al, 1969;Kasbekar, 1972) and cat in vivo (Hirst, 1988). The very transient nature of the response to pentagastrin has been noted in other studies in isolated stomach and gastric mucosa of the rat (Main & Pearce, 1978;Boughton-Smith & Whittle, 1981), but it appears less marked in other species, e.g. the mouse, ferret, cat and dog (Kuo & Shanbour, 1978;Yates et al, 1978;Black & Shankley, 1985).…”

“…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). 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).…”

Effects of indomethacin, piroxicam and selected prostanoids on gastric acid secretion by the rat isolated gastric mucosa

“…It is well established that prostaglandins, particularly of the E series, are potent inhibitors of gastric acid secretion in many species including rat (Frame & Main, 1980;Boughton-Smith & Whittle, 1981), dog (Robert et al, 1967) and man (Karim et al, 1973;Konturek et al, 1976). Although the inhibition of acid secretion in the rat is well documented no attempt has been made to classify the prostaglandin receptor mediating this response.…”

Effects of SCH 32651 on resting and stimulated acid secretion in guinea‐pig isolated fundic mucosa

“…As shown in Figure 8, and prostaglandin (Main & Pearce, 1978;Soll, 1980;Boughton-Smith & Whittle, 1981) in that it effectively abolishes the acid secretory responses by the fundic mucosa to the combination of db cyclic AMP and theophylline. This finding suggests that the site of action for SCH 32651 is distal to the adenylate cyclase-cyclic AMP system and presumably near or at the site of H+/K+-ATPase, which is localized at the apical and tubulovesical membranes of the parietal cell (Olbe et al, 1979;Fellenius et al, 1981;Ray & Fromm, 1981).…”