No contractile effect for 5‐HT 1D and 5‐HT 1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery

Using subtype‐selective 5‐HT 1 receptor agonists and/or the 5‐HT 1 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‐HT 1B 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‐HT 1 receptors in both species. In contrast, PNU‐109291 and LY344864, selective agonists at 5‐HT 1D and 5‐HT 1F 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‐HT 1 receptor antagonist GR127935 dose‐dependently inhibited the vasoconstrictions elicited by both 5‐HT and sumatriptan, with respective pA 2 values of 8.0 and 8.6. RT–PCR studies in human coronary arteries showed a strong signal for the 5‐HT 1B receptor while message for the 5‐HT 1F receptor was weak and less frequently detected. Expression of 5‐HT 1D 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‐HT 1B receptor, which is also present in a majority of human coronary arteries. These results suggest that selective 5‐HT 1D and 5‐HT 1F 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