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Pharmacological characterization of 5‐hydroxytryptamine receptor types in the guinea‐pig proximal colon
Author(s) -
BRIEJER M. R.,
AKKERMANS L. M. A.,
MEULEMANS A. L.,
LEFEBVRE R. A.,
SCHUURKES J. A. J.
Publication year - 1993
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.1993.tb00127.x
Subject(s) - tropisetron , ketanserin , granisetron , receptor antagonist , 5 ht receptor , chemistry , serotonin , receptor , pharmacology , tetrodotoxin , endocrinology , antagonist , medicine , biology , biochemistry , antiemetic , vomiting
It was investigated which 5‐hydroxytryptamine (5‐HT) receptors mediate the responses to 5‐HT in the longitudinal muscle layer of the guinea‐pig proximal colon, using selective 5‐HT receptor antagonists and the 5‐HT analogues α‐methyl‐5‐HT (2‐Me‐5‐HT), 2‐methyl‐5‐HT (2‐Me‐5‐HT), and 5‐methoxytryptamine (5‐MeOT). 5‐HT as well as its analogues induced concentration‐related contractions, at low concentrations preceded by relaxations. The 5‐HT concentration‐contractile response curve was biphasic whilst the curves to α‐Me‐5‐HT, 2‐Me‐5‐HT, and 5‐MeOT were monophasic. Tetrodotoxin (TTX) abolished the relaxations, and it inhibited the contractions to all agonists. In the presence of TTX, blockade of either 5‐HT 2 (ketanserin) or 5‐HT 3 receptors (ondansetron, tropisetron) reduced the contractions to 5‐HT, whereas blockade of both 5‐HT receptor types at the same time abolished them. In the absence of TTX, the contractions to 5‐HT were inhibited by antagonists at 5‐HT 2 (ketanserin), 5‐HT 3 (granisetron, nanomolar concentration of tropisetron) and also 5‐HT 4 receptors (micromolar concentration of tropisetron). Contractions to α‐Me‐5‐HT did not seem to be sensitive to 5‐HT 2 receptor blockage with ketanserin, but in the presence of TTX the contractions were abolished by the 5‐HT 2 receptor antagonist. The 5‐HT 3 receptor antagonist granisetron abolished contractions to 2‐Me‐5‐HT. In the presence of TTX, the 5‐HT 2 receptor antagonist ketanserin abolished contractions to 5‐MeOT, and in the absence of TTX the contractions to 5‐MeOT were highly sensitive blockade of 5‐HT 4 receptors with tropisetron. Blockage of either 5‐HT 1 (methiothepin), 5‐HT 2 (ketanserin), 5‐HT 3 (ondansetron, granisetron, tropisetron) or 5‐HT 4 (tropisetron) receptors did not abolish the relaxations to 5‐HT or 5‐MeOT. In conclusion, 5‐HT induces contractions of the longitudinal muscle of the guinea‐pig proximal colon, through the stimulation of 5‐HT 2 receptors on the smooth muscle cells and 5‐HT 3 receptors and putative neuronal 5‐HT 4 receptors. 5‐HT evokes relaxations via an unknown neuronal receptor.