title: No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery.
abstract: 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 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). 2. 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. 3. 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. 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 frequently detected. Expression of 5-HT1D receptor mRNA was not detected in any sample. 5. 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.
authors.affiliation: Laboratory of Cerebrovascular Research, Montréal Neurological Institute, McGill University, Québec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Bouchelet
authors.forename: B
authors.initials: B
authors.lastname: Case
authors.forename: A
authors.initials: A
authors.lastname: Olivier
authors.forename: E
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation; D012333:RNA, Messenger / Q000096:biosynthesis; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D000096642:Receptor, Serotonin, 5-HT1F
chemical_list: D012333:RNA, Messenger; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D018170:Sumatriptan; D000096642:Receptor, Serotonin, 5-HT1F