Invited Symposium: Cerebral Artery Pharmacology and Physiology
Bogdan Sima, B (Department of Neurosurgery, University of Chicago, USA)
MacDonald, RL (Department of Neurosurgery, University of Chicago, USA)
Weir, B (Department of Neurosurgery, University of Chicago, USA)
Extracellular nucleotides play an important role in the regulation of cerebral vascular tone and may be involved in cerebrovascular disorders such as vasospasm after subarachnoid hemorrhage. The P2 receptor subtypes and their activation-mediated [Ca2+]i elevation and cerebral arterial contraction have been investigated. Extracellular nucleotides produced a concentration dependent biphasic [Ca2+]i response, and the potency of nucleotides to raise [Ca2+]i was ATPyS greater than UDP greater than ATP equal to UDP equal to TTP greater than ADP greater AMP equal to a,B-methylene-ATP equal to 2-SATP greater than adenosine, indicating that P2u receptors were expressed in the rat basilar smooth muscle cells. The effect of UTP, a selective agonist for the P2u receptor, to release Ca2+ from internal stores was reduced by pertussis toxin, by the phospholipase C(PLC) inhibitor 2-nitro-4-carboxyphenyl N, N-diphenylcarbamate (NCDC), and by the Ca2+ -pump inhibitor thapsigargin. The Ca2+ entry induced by UTP was partially attenuated by the receptor-operated Ca2+ channel blocker SK&F 96365, and by the voltage-dependent Ca2+ channel blocker verapamil. P2 receptor antagonists, suramin and, at higher concentrations, PPADS, reduced the effect of UTP. ATP and UPT produced concentration dependent contraction in dog basilar artery and their effect were reduced by suramin. These results demonstrated that nucleotides activate G-protein coupled P2u receptors to mobilize [Ca2+]i and produce contraction in cerebral arteries.
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|Zhang, J; Bogdan Sima, B; MacDonald, RL; Weir, B; (1998). P2 Receptors In Cerebral Arteries. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/laher/zhang0702/index.html|
|© 1998 Author(s) Hold Copyright|