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

1 Using subtype-selective 5-HT1 receptor agonists and/or the 5-HT1 receptor antagonist GR127935, we characterized in vitro the 5-HT receptor that medi ates the contraction of human and bovine cerebral arteries. Further, we inv estigated which sumatriptan-sensitive receptors are present in human corona ry artery by reverse-transcriptase polymerase chain reaction (RT-PCR). 2 Agonists with affinity at the 5-HT1B receptor, such as sumatriptan, alnid itan and/or IS-159, elicited dose-dependent contraction in both human and b ovine cerebral arteries. They behaved as full agonists at the sumatriptan-s ensitive 5-HT1 receptors in both species. In contrast, PNU-109291 and LY344 864, 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. 3 In bovine cerebral arteries, the 5-HT1 receptor antagonist GR127935 dose- dependently inhibited the vasoconstrictions elicited by both 5-HT and sumat riptan, with respective pA(2) values of 8.0 and 8.6. 4 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 fre quently detected. Expression of 5-HT1D receptor mRNA was not detected in an y sample. 5 The present results demonstrate that the triptan-induced contraction in b rain vessels is mediated exclusively by the 5-HT1B receptor, which is also present in a majority of human coronary arteries. These results suggest tha t selective 5-HT1D and 5-HT1F receptor agonists might represent new antimig raine drugs devoid of cerebro- and cardiovascular effects.