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Characterization of the receptors involved in the 5‐HT‐induced excitation of canine antral longitudinal muscle
Author(s) -
Prins N H,
Akkermans L M A,
Lefebvre R A,
Schuurkes J A J
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704376
Subject(s) - methysergide , agonist , endocrinology , medicine , 5 ht receptor , receptor antagonist , chemistry , receptor , atropine , serotonin , tetrodotoxin , antagonist , biology
We aimed to characterize the 5‐HT receptors involved in the 5‐HT‐induced effect on electrically induced contractions of dog antrum longitudinal muscle in vitro . In the presence of L ‐NOARG (0.1 m M ), electrical field stimulation (EFS) induced atropine‐ and tetrodotoxin‐sensitive contractions. Tetrodotoxin or atropine left any agonist tested ineffective. These EFS‐induced contractions were on average enhanced by 5‐HT (0.3 μ M ), however, pronounced variation in the response to 5‐HT was observed. There were non‐significant trends of the selective 5‐HT 3 receptor antagonist granisetron (1 μ M ), and methysergide (1 μ M ; preventing interactions of 5‐HT with 5‐HT 1 , 5‐HT 2 , 5‐ht 5 , 5‐HT 6 and 5‐HT 7 receptors) to increase the response to 5‐HT. The selective 5‐HT 4 receptor antagonist GR 113808 (0.1 μ M ) displayed a non‐significant trend to inhibit the 5‐HT‐induced increase. Combination experiments with methysergide (1 μ M ), granisetron (1 μ M ) and GR 113808 (0.1 μ M ) revealed that the 5‐HT (0.3 μ M )‐induced response consisted of (1) an excitatory component blocked by GR 113808, (2) excitatory and inhibitory components both blocked by methysergide. The selective 5‐HT 4 receptor agonist prucalopride (0.3 μ M ) increased EFS‐induced contractions, an effect prevented by GR 113808 (0.1 μ M ). The increase of EFS‐induced contractions by the preferential 5‐HT 2 receptor agonist α‐Me‐5‐HT (0.3 μ M ) was antagonized by 5‐HT 2B receptor antagonists. The 5‐HT 1 /5‐HT 7 receptor agonist 5‐carboxamidotryptamine (5‐CT; 0.3 μ M ) inhibited EFS‐induced contractions. This was prevented by methysergide (1 μ M ), the 5‐HT 7 receptor antagonist mesulergine (0.3 μ M ) and the selective 5‐HT 7 receptor antagonist SB‐269970 (0.3 μ M ). In the presence of GR 113808 (0.1 μ M ), α‐Me‐5‐HT (1 μ M ) increased EFS‐induced contractions. The 5‐HT (0.3 μ M )‐induced inhibition of the stimulation by α‐Me‐5‐HT was prevented by SB‐269970 (0.3 μ M ). In conclusion, dog antral longitudinal muscle is endowed with (1) excitatory neuronal 5‐HT 4 receptors and 5‐HT 2B receptors and (2) inhibitory smooth muscle 5‐HT 7 receptors.British Journal of Pharmacology (2001) 134 , 1351–1359; doi: 10.1038/sj.bjp.0704376