No contractile effect for 5‐HT1D and 5‐HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery

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Abstract
Using subtype‐selective 5‐HT1 receptor agonists and/or the 5‐HT1 receptor antagonist GR127935, we characterized in vitro the 5‐HT receptor that mediates the contraction of human and bovine cerebral arteries. Further, we investigated which sumatriptan‐sensitive receptors are present in human coronary artery by reverse‐transcriptase polymerase chain reaction (RT–PCR). Agonists with affinity at the 5‐HT1B receptor, such as sumatriptan, alniditan and/or IS‐159, elicited dose‐dependent contraction in both human and bovine cerebral arteries. They behaved as full agonists at the sumatriptan‐sensitive 5‐HT1 receptors in both species. In contrast, PNU‐109291 and LY344864, selective agonists at 5‐HT1D and 5‐HT1F receptors, respectively, were devoid of any significant vasocontractile activity in cerebral arteries, or did not affect the sumatriptan‐induced vasocontraction. The rank order of agonist potency was similar in both species and could be summarized as 5‐HT=alniditan>sumatriptan=IS‐159>>>PNU‐109291=LY344864. In bovine cerebral arteries, the 5‐HT1 receptor antagonist GR127935 dose‐dependently inhibited the vasoconstrictions elicited by both 5‐HT and sumatriptan, with respective pA2 values of 8.0 and 8.6. RT–PCR studies in human coronary arteries showed a strong signal for the 5‐HT1B receptor while message for the 5‐HT1F receptor was weak and less frequently detected. Expression of 5‐HT1D receptor mRNA was not detected in any sample. The present results demonstrate that the triptan‐induced contraction in brain vessels is mediated exclusively by the 5‐HT1B receptor, which is also present in a majority of human coronary arteries. These results suggest that selective 5‐HT1D and 5‐HT1F receptor agonists might represent new antimigraine drugs devoid of cerebro‐ and cardiovascular effects. British Journal of Pharmacology (2000) 129, 501–508; doi:10.1038/sj.bjp.0703081

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