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5‐HT 1 ‐like receptors mediate 5‐hydroxytryptamine‐induced contraction of guinea‐pig isolated iliac artery
Author(s) -
SahinErdemli I.,
Hoyer D.,
Stoll A.,
Seiler M.P.,
Schoeffter P.
Publication year - 1991
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 - 10.1111/j.1476-5381.1991.tb12183.x
Subject(s) - ketanserin , medicine , endocrinology , chemistry , sumatriptan , antagonist , receptor antagonist , 5 ht receptor , competitive antagonist , pargyline , receptor , agonist , serotonin , pharmacology
1 The effects of 5‐hydroxytryptamine (5‐HT) and of the 5‐HT 1 ‐like receptor agonists, 5‐carboxamidotryptamine (5‐CT) and sumatriptan (GR43175) were investigated in isolated ring preparations of guinea‐pig common iliac artery. 2 The three agonists induced very weak, if any, contractions of unstimulated preparations, whereas they elicited concentration‐dependent contractions in preparations given a moderate tone by a threshold concentration of prostaglandin F 2α (PGF 2α ). 3 Under the latter conditions, E max values for 5‐HT and 5‐CT reached about 45% of PGF 2α maximal effect, whereas the E max value of sumatriptan was significantly lower (about 35%). The rank order of potency (mean EC 50 value, n m ) was 5‐CT (6.6) > 5‐HT (22.9) > sumatriptan (155). Pargyline, cocaine or deoxycorticosterone were without significant effect on the contractions induced by 5‐HT. 4 The 5‐HT 3 receptor antagonist, (1αH,3α,5αH‐tropan‐3‐yl) 1‐H‐indole‐3‐carboxylic acid ester (ICS 205–930; 1 μ m ), had no effect on 5‐HT‐, 5‐CT‐ and sumatriptan‐induced contractions. 5 The 5‐HT 2 receptor antagonist, ketanserin (1 μ m ) caused only small rightward shifts (concentration‐ratios, about 2) in the concentration‐response curves to 5‐HT, 5‐CT and sumatriptan without significantly depressing the maximum effects. 6 In the presence of ketanserin (1 μ m ), the non‐selective 5‐HT receptor antagonist, methiothepin (0.1 μ m ), shifted the concentration‐response curves to 5‐HT and 5‐CT to the right in a parallel manner and to a similar extent for both agonists (respective mean pK B values, 8.07 and 8.27). The effect of sumatriptan was also antagonized by methiothepin, but solvent effects precluded quantitative analysis of this antagonism. 7 It is concluded that 5‐HT 1 ‐like receptors mediate the contractions induced by 5‐HT, 5‐CT and sumatriptan in guinea‐pig isolated iliac artery. For reasons not yet understood, these receptors are detected only when the tissues are moderately pre‐contracted by PGF 2α .