Expression of mRNA for the serotonin 5-hydroxytryptamine1D beta receptor subtype in human and bovine cerebral arteries

E Hamel, E Fan, D Linville, V Ting, JG Villemure and LS Chia

Cerebrovascular Research Laboratory, McGill University, Montreal, Quebec, Canada.

Serotonin [5-hydroxytryptamine (5-HT)] has been implicated in the pathophysiology of migraine, and the clinical efficacy of the 5-HT1B/5- HT1D receptor agonist sumatriptan points to neural and/or vascular 5- HT1D receptors as relevant targets in migraine therapy. We characterized the human and/or bovine 5-HT1D receptor subtype in cerebral blood vessels pharmacologically by correlation analysis and molecularly by Northern blot hybridization of cerebrovascular RNA extracts. Pharmacological analysis showed that sumatriptan was less potent than 5-HT in inducing contraction in freshly isolated human cerebral arteries and revealed an overall pharmacological profile positively and significantly correlated with that published for the 5- HT1D alpha (r = 0.746, p = 0.021) and 5-HT1D beta (r = 0.942, p = 0.0001) cloned human receptor subtypes. These results are suggestive of a contractile 5-HT1D beta receptor subtype but are not conclusive. However, Northern blots revealed the presence of mRNA transcripts for the 5-HT1D beta subtype, but not the 5-HT1D alpha subtype, in bovine (approximately 2.2 kilobases) and human (approximately 4.5 kilobases) cerebral blood vessels. Expression of either subtype could not be detected in intraparenchymal microvessels or capillaries isolated from bovine or human cerebral cortex. These results clearly indicate that the beneficial effect of sumatriptan in migraine attack, if vascularly related, is mediated by contractile 5-HT1D beta receptors most likely located on cerebral blood vessels at the surface of the brain. This study points to the 5-HT1D beta receptor subtype as the putative cerebrovascular target for migraine therapeutic agents.

Volume 44, Issue 2, pp. 242-246, 08/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				A. M. VanDenBrink, R. W. M. van den Broek, R. de Vries, A. J. J. C. Bogers, C. J. J. Avezaat, and P. R. Saxena Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels Neurology, November 28, 2000; 55(10): 1524 - 1530. [Abstract] [Full Text] [PDF]

				T. Ishine, I. Bouchelet, E. Hamel, and T. J. F. Lee Serotonin 5-HT7 receptors mediate relaxation of porcine pial veins Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H907 - H912. [Abstract] [Full Text] [PDF]

				M. L. Cohen and K. Schenck 5-Hydroxytryptamine1F Receptors Do Not Participate in Vasoconstriction: Lack of Vasoconstriction to LY344864, a Selective Serotonin1F Receptor Agonist in Rabbit Saphenous Vein J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 935 - 939. [Abstract] [Full Text]

				G. W. John, P. J. Pauwels, M. Perez, S. Halazy, B. Le Grand, Y. Verscheure, J.-P. Valentin, C. Palmier, T. Wurch, P. Chopin, et al. F 11356, a Novel 5-Hydroxytryptamine (5-HT) Derivative with Potent, Selective, and Unique High Intrinsic Activity at 5-HT1B/1D Receptors in Models Relevant to Migraine J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 83 - 95. [Abstract] [Full Text]

				J. R. Smith, C. Kim, H. Kim, and R. E. Purdy Precontraction with Elevated Concentrations of Extracellular Potassium Enables both 5-HT1B and 5-HT2A "Silent" Receptors in Rabbit Ear Artery J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 354 - 360. [Abstract] [Full Text]

				T. Ishida, K.-i. Hirata, T. Sakoda, S. Kawashima, H. Akita, and M. Yokoyama Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries Cardiovasc Res, January 1, 1999; 41(1): 267 - 274. [Abstract] [Full Text] [PDF]

				G. Q. Teng, J. Williams, L. Zhang, R. Purdy, and W. J. Pearce Effects of maturation, artery size, and chronic hypoxia on 5-HT receptor type in ovine cranial arteries Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1998; 275(3): R742 - R753. [Abstract] [Full Text] [PDF]

				H. Movahedi and R. E. Purdy Pharmacological Characterization of the "Silent" 5-Hydroxytryptamine1B-like Receptors of Rabbit Ear Artery J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 653 - 660. [Abstract] [Full Text]

				M. A. Moskowitz and C. Waeber Migraine Enters the Molecular Era Neuroscientist, May 1, 1996; 2(3): 191 - 200. [Abstract] [PDF]