Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinea-pig ileum. Evidence for two distinct release mechanisms.

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)