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5‐HT 1B receptor‐mediated contractions in human temporal artery: evidence from selective antagonists and 5‐HT receptor mRNA expression
Author(s) -
Verheggen R.,
Hundeshagen A. G.,
Brown A. M.,
Schindler M.,
Kaumann A. J.
Publication year - 1998
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.0701929
Subject(s) - ketanserin , receptor , 5 ht receptor , receptor antagonist , 5 ht1 receptor , pharmacology , serotonin , antagonist , chemistry , 5 ht2 receptor , endocrinology , medicine , biology , biochemistry
1 In the human temporal artery both 5‐HT 1‐like and 5‐HT 2A receptors mediate the contractile effects of 5‐hydroxytryptamine (5‐HT) and we have suggested that the 5‐HT 1‐like receptors resemble more closely recombinant 5‐HT 1B than 5‐HT 1D receptors. To investigate further which subtype is involved, we investigated the blockade of 5‐HT‐induced contractions by the 5‐HT 1B ‐selective antagonist SB‐224289 (2,3,6,7‐tetrahydro‐1′‐methyl‐5‐{2‐methyl‐4′[(5‐methyl‐1,2,4‐oxadiazole‐3‐yl) biphenyl‐4‐yl] carbonyl} furo[2,3‐f]indole‐3‐spiro‐4′‐piperidine oxalate) and the 5‐HT 1D ‐selective antagonist BRL‐15572 (1‐phenyl‐3[4‐3‐chlorophenyl piperazin‐1‐yl] phenylpropan‐2‐ol). We also used RT‐PCR to search for the mRNA of 5‐HT 1B , 5‐HT 1D and other 5‐HT receptors. 2 The contractile effects of 5‐HT in temporal artery rings were partially antagonized by SB‐224289 (20, 200 n m ) (apparent K B = 1 n m ) and ketanserin (1 μ m ) but not by BRL‐15572 (500 n m ). 3 Sumatriptan evoked contractions (EC 50 , 170 n m ) that were resistant to blockade by BRL‐15572 (500 n m ) but antagonized by SB‐224289 (20, 200 n m ). 4 The potency of 5‐HT (EC 50 ) was estimated to be 94 n m for the ketanserin‐sensitive receptor and 34 n m for the SB‐224289‐sensitive receptor. The fraction of maximal 5‐HT response mediated through SB‐224289‐sensitive receptors was 0.20–0.67, the remainder being mediated through ketanserin‐sensitive receptors. 5 We detected arterial receptor mRNA for the following receptors (incidence): 5‐HT 1B (8/8), 5‐HT 1D (2/8), 5‐HT 1F (0/4), 5‐HT 2A (0/8), 5‐HT 2B (0/8), 5‐HT 2C (0/8), 5‐HT 4 (4/8) and 5‐HT 7 (4/8). 6 We conclude that the ketanserin‐resistant fraction of the 5‐HT effects and the effects of sumatriptan are mediated by 5‐HT 1B receptors. The lack of antagonism by BRL‐15572 rules out 5‐HT 1D receptors as mediators of the contractile effects of 5‐HT and sumatriptan.British Journal of Pharmacology (1998) 124 , 1345–1354; doi: 10.1038/sj.bjp.0701929