Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinea-pig ileum

Abstract

The contractile effect of 5-HT in the isolated longitudinal ileal muscle of adult guinea-pigs was studied over a large concentration range. 5-HT produced a biphasic concentration-response curve indicative of an interaction with at least two independent populations of receptors. The concentrations which elicited half-maximal effects for the first and the second phases of the concentration-response curve were estimated as 1.5 +/- 1.2 X 10(-8) mol/l and 1.3 +/- 0.4 X 10(-6) mol/l respectively. The maximal response produced by the interaction of 5-HT with the high affinity receptor (i.e. first phase) was calculated as 27 +/- 9.3% of the total response. The biphasic concentration-response was not influenced by methysergide (10(-6) mol/l). The effect of low concentrations of 5-HT (less than 3 X 10(-7) mol/l) was antagonised by atropine (10(-7) mol/l), tetrodotoxin (TTX) (10(-6) mol/l), morphine (10(-5) mol/l), the substance P antagonist, D-Pro4,D-Trp7,9-SP4-11 (3 X 10(-5) mol/l) and capsaicin (10(-5) mol/l). Physostigmine (10(-7) mol/l) augmented the effect. The response to high concentrations of 5-HT (3 X 10(-7)-3 X 10(-6) mol/l) was antagonised by ICS 205-930 and D-Pro4,D-Trp7,9-SP4-11 in a competitive manner and was inhibited by TTX, morphine and capsaicin in an insurmountable way. The effect of very high concentrations of 5-HT (greater than 10(-5) mol/l) could be partially antagonised by methysergide (10(-7) mol/l) in the presence of ICS 205-930 (10(-7) mol/l) and totally by a combination of methysergide and TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

“…It is known that agonists of the 5-HT receptors increase the release of acethylcholine from the motor nerve ending within the intestinal muscle and facilitate peristalsis and may be involved in mechanismsat 5-HT 3 receptors (35)(36)(37). However, in the present study granisetron at a concentration as high as 1.0 µM failed to significantly modify relaxation and contractile responses to EFS.…”

Species Differences in the 5-Hydroxytryptamine-Induced Contraction in the Isolated Distal Ileum.

“…It was suggested that both neuronal and non-neuronal 5-HT receptors in the lon gitudinal muscle of guinea pig ileum were involved in the 5-HT-induced contraction (1)(2)(3)(4)(5)(6)(7)(8). Although the nature of the non-neuronal 5-HT receptor remains unclear, the neuronal 5-HT receptor was defined as the 5-HT3 and 5 HT4 receptor subtypes which mediated acetylcholine re lease (7).…”

“…In the gastrointestinal tract, 5-HT is reported to contribute to the regulation of the motility and secretion via several 5-HT-receptor subtypes. The in volvement of the 5-HT-receptor subtype in 5-HT-induced intestinal contraction has been well-examined in the guinea pig small and large intestines (1)(2)(3)(4)(5)(6)(7)(8). In contrast, the effect of 5-HT on the regulation of intestinal motility has not been established in species other than guinea pigs.…”

Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

“…In this study, ICS-205-930 strongly inhibited EM523 as well as motilin-induced gas tric contractions. 5HT3 receptors are reported to be dis tributed in the area postrema (12)(13)(14), the enteric nervous system (15)(16)(17) and afferent vagus nerves (14,17,18) in ferrets, rats and guinea pigs. Boeckxstaens et al (19) reported that stimulation of the 5HT3 receptors resulted in acetylcholine-mediated contractions through choliner gic efferent nerves in the canine ileal myenteric plexus.…”