A tachykinin antagonist inhibits gastric emptying and gastrointestinal transit in the rat

Abstract

1 The effect of a substance P antagonist, [D-Pro2, D-Trp7' 1-substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 5'Cr.2 Examination 15 min after the test meal showed that SPA (0.13-1.3 Amol kg-') inhibited gastric emptying and gastrointestinal transit in a dose-dependent manner. 3 The inhibitory effect of SPA on gastric emptying and gastrointestinal transit remained unchanged after pretreatment of rats with mepyramine (8.7 pimol kg-') plus cimetidine (19.8 pmol kg-') or with guanethidine (67 ttmol kg-'). 4 Since a full examination of SPA as a specific tachykinin antagonist was not possible in vivo, SPA was also tested on circular muscle strips from the rat gastric corpus in vitro. Submaximal contractions in response to bombesin or bethanechol were not reduced by SPA (50 fLM), whereas those in response to substance P were inhibited. 5 The results suggest that SPA inhibits gastric emptying and gastrointestinal transit by interfering with the action of tachykinins released from enteric nerves and that endogenous tachykinins are involved in the regulation of gastrointestinal motility.

Endotoxin inhibits gastric emptying in rats via a capsaicin-sensitive afferent pathway

“…In the present study neither systemic pre-treatment with capsaicin nor blockade of CGRP receptors modified the rate of GE in control animals, suggesting that the afferent type C nervous fibers are not involved in the physiological control of gastric emptying of a solid nutrient meal in conscious animals, as stated in previous reports (Holzer 1986a). However, selective blockade of tachykinins receptors with D-Pro 2 , D-Trp 7,9 -substance P did significantly decrease GE, as previously reported (Holzer 1986b), suggesting a role for these neuropeptides in the control of gastric emptying. There are various possible explanations for the apparent discrepancy between capsaicin pre-treatment and blockade of tachykinins receptors: (a) endogenous tachykinins involved in the physiology of gastric emptying may originate from capsaicin-insensitive nerves (Holzer 1988); (b) chronic treatment with capsaicin vs. acute administration of the receptor antagonist could induce compensatory mechanisms that mask the role of tachykinins on GE.…”

Comparison of Two Orogastric Feeding Markers for Measuring Gastrointestinal Motor Functions in Rats

“…Our charcoal transit ratios at some experimental periods were compatible with previous stud ies [1,2], Therefore our techniques included the opening of the abdomen and removal of the gut to measure whether transit values were reliable. Indeed, this measuring model never displaces that of the feeding of fluid within the small intestine [8], The leading front of char coal advancing within the small intestine has been extensively used as a standard procedure to measure intestinal transit [1][2][3]10]. We observed that radiochromium always reached the most distal small intestinal segment irre spective of the experimental periods.…”

Irritable bowel syndrome: Present and prospective pharmacological intervention

“…As this is probably mediated via a*-adrenoreceptors, agonists, like clonidine, that are selective for this subtype of receptor might be expected to be particularly applicable. Blockade of transmitters, such as acetylcholine, substance P, 44 and VIP, that stimulate secretory mechanisms by crypt cells is also possible. This would have the added advantage of antagonizing the same neurotransmitters that excite at the level of the myenteric plexus.…”