Summary1. Isoprenaline (002 to 2-0 ,ug kg-' min-') inhibited gastric secretion in response to pentagastrin in both conscious and anaesthetized dogs and in response to feeding in conscious dogs.2. The inhibition was unaffected during cardiac f8-adrenoceptor blockade by propranolol. 3. The inhibition was not due to decreased mucosal blood flow. 4. This effect of isoprenaline is different from its effect on histamine-induced gastric secretion. 5. Noradrenaline (005-2-0 ,ug kg-' min') also decreased gastric secretion but it was less effective than isoprenaline. 6. The mechanism of action of noradrenaline is probably a decrease in mucosal blood flow.
IntroductionThe effect of an adrenoceptor stimulant drug on gastric secretion depends on many factors, particularly whether it acts on a-or ,8-receptors and whether secretion is induced by histamine or by gastrin-like compounds. This field has recently been reviewed by Holton (1972). The mechanism of action of noradrenaline, an .a-adrenoceptor agonist, appears to be primarily by the production of a decrease in mucosal blood flow (Jacobson, 1970). The mechanism of action of the 3-adrenoceptor agonist, isoprenaline, is more complex. On a background of histamine stimulation, small doses of isoprenaline increase or do not affect secretion
SUMMARY1. Methods for the estimation of radioactive aniline in body fluids are described. The recovery of aniline added to blood, plasma and gastric juice was over 90 % of the recovery from saline.2. In the doses used aniline caused methaemoglobinaemia of 5-11 % of total haemoglobin. No other effect was detected. Gastric secretion was also unaffected. 3. Aniline clearance increased in parallel with acid secretion from Heidenhain pouches in conscious dogs and in anaesthetized dogs. In conscious dogs the ratio of aniline clearance to acid secretion was significantly higher for histamine stimulation than for pentagastrin stimulation.4. Aniline and amidopyrine clearances were compared simultaneously in the same dogs. Aniline clearance was about 80 % of amidopyrine clearance.5. The proportion of aniline bound to plasma proteins was measured by two methods and found to be 25 %. When aniline clearance was corrected for plasma binding, aniline and amidopyrine clearances were equal.
1 The effects of the mast-cell stabilizing agent, FPL 52694, on gastric acid secretion in conscious dogs with gastric fistulae have been studied. 2 FPL 52694 (5 or 10mg kgl h-) given intravenously during a plateau response to pentagastrin stimulation (21ggkg-I h-1) caused a maximum inhibition of acid output of about 50% but had no significant effect on volume output so that the [H+] in the juice was markedly reduced. The ratio of mucosal blood flow/acid output (Ra) was increased in the presence of FPL 52694. There was no maintained reduction of [H+] when inhibition was due to cimetidine (41mol kg-', i.v.).3 Instillation of FPL 52694 (4.35 mg ml-l) directly into the stomach via the fistula for 30 min also resulted in an inhibition of acid output and reduction of [HI] during both pentagastrin-(2 pg kg-l h-1) and histamine-stimulated (301 g kg-l h-1) secretion. Inhibition of pentagastrinstimulated acid output by intragastric administration of FPL52694 was much greater than the maximum effect seen following intravenous infusion. 4 The results are discussed in relation to the possible mode of action of FPL 52694. It is concluded that FPL 52694 is active orally and has a novel action on acid secretion which may include stimulation of gastric bicarbonate secretion.
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