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Reliable Isolation of Central Nervous System Microvessels Across Five Vertebrate Groups
Published on: January 12, 2020
Functional serotonin and histamine receptor subtypes in porcine ciliary artery in comparison with middle cerebral
Shingo Nagai1, Tatsuru Tsurumaki, Haruki Abe
1Division of Pharmacology, Department of Molecular Genetics and Signal Transduction Research, Course for Molecular and Cellular Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
Abstract:
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.
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