The Sites of Action of 5-Hydroxytryptamine in Nerve-Muscle Preparations From the Guinea-Pig Small Intestine and Colon

Abstract

1 The sites of action of 5-hydroxytryptamine (5-HT) were examined in isolated segments of guineapig intestine. Mechanical records were taken from the longitudinal muscle of the ileum and proximal colon and from the circular muscle of the ileum and distal colon. 2 In order to examine direct actions of 5-HT, nerve-mediated responses were blocked with tetrodotoxin (0.2 jig/ml). There was a gradient in the responsiveness of the longitudinal muscle of the ileum; in the proximal ileum it was usually unresponsive, whereas in the distal ileum about 30% of the amplitude of contraction was caused by a direct effect on the muscle. In the circular muscle from all parts of the ileum, direct effects on the muscle were weak or absent. In the distal colon, the circular muscle was almost always unresponsive to direct effects of 5-HT even when concentrations of 5-HT as great as 100 pg/ml were used. All direct actions of 5-HT on intestinal muscle were blocked by methysergide (1 jig/ml), which itself did not affect nerve-mediated responses.3 Excitatory cholinergic nerves and excitatory and inhibitory nerves which released unidentified substances were all stimulated by 5-HT. The contractions mediated through cholinergic nerves were blocked by hyoscine (0.6 jg/ml). 4 Tachyphylaxis to the action of 5-HT occurred both for effects mediated through nerves and for direct effects on the muscle. Responses returned promptly after 5-HT was washed from the organ bath.5 While 5-HT blocked its own action on neural receptors, it did not antagonize the stimulation of nicotinic receptors on cholinergic neurones by 1-1 dimethyl-4-phenylpiperazinium iodide (DMPP). Moreover, pentolinium markedly reduced contractions caused by DMPP without significantly affecting responses to 5-HT. In contrast, (+)tubocurarine, another nicotinic receptor antagonist, was effective in reducing contractions caused by 5-HT. 6 Phenyldiguanide, which has been reported to antagonize the stimulant action of 5-HT on cholinergic neurones in the mouse small intestine, did not cause any significant reduction in the action of 5-HT on cholinergic neurones in the guinea-pig ileum unless a concentration of 1 mg/ml was used. However, contractions elicited by carbachol and DMPP were antagonized to a similar extent by phenyldiguanide at this concentration. Antagonism of the action of 5-HT at neural receptors by bromolysergic acid and by tryptamine was found but it was not specific, these drugs causing comparable decreases in responses to 5-HT, carbachol and DMPP. 7 The present results, which show that 5-HT has little or no direct effect on the circular muscle of the ileum and colon, imply that, if 5-HT is a transmitter in enteric reflexes, it must be released from interneurones.

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.…”

Four motor effects of capsaicin on guinea‐pig distal colon

“…A 1.0-1.5 cm long segment of the proximal part of the hypogastric loop of the distal colon was rapidly dissected out and placed in oxygenated (96% 02 plus 4% CO2) physiological salt solution (PSS), of the following composition (mM): NaCl 119, NaHCO3 25, KCI 4.7, MgSO41.2, KH2PO4 1.2, CaCl22.5, glucose 11. The segments were suspended, in an oxygenated solution contained in a 5 ml organ bath and connected to an isometric strain gauge and a Basile 7050 recorder in such a way as to register movements ofthe longitudinal muscle, as described by Costa & Furness (1979). Bath temperature was maintained at 37°C.…”

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

“…However at the higher concentration of 1.0 µM, ritanserin diminished EFS-induced contractions recorded from the rat intestine. It has been shown that the 5-HT 2 receptors are involved in mediating a contraction response to the exogenously added 5-HT, following the administration of 10 nM -0.1 µM ritanserin which could reliably block 5-HT 2 receptors in theGIT of different species (31)(32)(33). Also, in in vitro binding assays in brain tissue (34), the antagonism by ritanserin was achieved at concentrations in the nanomolar range.…”