Functional serotonin and histamine receptor subtypes in porcine ciliary artery in comparison with middle cerebral artery.
Functional serotonin (5-HT) and histamine receptor subtypes were investigated in porcine middle cerebral and ciliary arteries. An H(1) antagonist, mepyramine, antagonized histamine-induced responses with pK(B) values of 8.91-9.10. In the presence of 1 muM mepyramine, however, histamine caused dilation through H(2) receptors in the middle cerebral but not in the ciliary artery. A 5-HT(2A) antagonist, ketanserin, antagonized 5-HT-induced responses, causing rightward shifts in the concentration-response curves with pK(B) values of 8.52-8.71. A 5-HT(1B) antagonist, SB224289, produced rightward shifts of the concentration-response curves to sumatriptan with pK(B) values (6.66) only in the middle cerebral artery. In contrast, a 5-HT(1D) antagonist, BRL15572, had no effect in either artery. An RT-PCR study demonstrated the gene expression of the mRNAs of all three receptors (5HT(1B), 5HT(1D) and 5HT(2A)) in both arteries. These results suggest that histamine-induced contraction is mediated only through functional H(1) receptor in these arteries. Interestingly, there are functional 5-HT(2A) and 5-HT(1B) receptor subtypes in the middle cerebral artery, whereas the only functional receptor is 5-HT(2A) in the ciliary artery. The difference may be important for treatment with 5-HT(1B/1D) agonists (e.g. for migraine) without ocular side effect.
Nagai
Shingo
S
Division of Pharmacology, Department of Molecular Genetics and Signal Transduction Research, Course for Molecular and Cellular Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
Tsurumaki
Tatsuru
T
Abe
Haruki
H
Higuchi
Hiroshi
H
D000818:Animals; D019842:Ciliary Arteries / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011968:Receptors, Histamine / Q000502:physiology*; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013552:Swine
D017442:Histamine Agonists; D006633:Histamine Antagonists; D012333:RNA, Messenger; D011968:Receptors, Histamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006632:Histamine