5‐HT1B receptor‐mediated contractions in human temporal artery: evidence from selective antagonists and 5‐HT receptor mRNA expression

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Abstract
1 In the human temporal artery both 5‐HT1‐like and 5‐HT2A receptors mediate the contractile effects of 5‐hydroxytryptamine (5‐HT) and we have suggested that the 5‐HT1‐like receptors resemble more closely recombinant 5‐HT1B than 5‐HT1D receptors. To investigate further which subtype is involved, we investigated the blockade of 5‐HT‐induced contractions by the 5‐HT1B‐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‐HT1D‐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‐HT1B, 5‐HT1D and other 5‐HT receptors. 2 The contractile effects of 5‐HT in temporal artery rings were partially antagonized by SB‐224289 (20, 200 nm) (apparent KB = 1 nm) and ketanserin (1 μm) but not by BRL‐15572 (500 nm). 3 Sumatriptan evoked contractions (EC50, 170 nm) that were resistant to blockade by BRL‐15572 (500 nm) but antagonized by SB‐224289 (20, 200 nm). 4 The potency of 5‐HT (EC50) was estimated to be 94 nm for the ketanserin‐sensitive receptor and 34 nm 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‐HT1B (8/8), 5‐HT1D (2/8), 5‐HT1F (0/4), 5‐HT2A (0/8), 5‐HT2B (0/8), 5‐HT2C (0/8), 5‐HT4 (4/8) and 5‐HT7 (4/8). 6 We conclude that the ketanserin‐resistant fraction of the 5‐HT effects and the effects of sumatriptan are mediated by 5‐HT1B receptors. The lack of antagonism by BRL‐15572 rules out 5‐HT1D 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

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