(Stroke. 1997;28:2053-2059.)
© 1997 American Heart Association, Inc.
Articles |
From the Section of Neurosurgery, Department of Surgery, University of Chicago (Ill).
Correspondence to H. Zhang, MD, PhD, Deborah Research Institute, 20 Pine Mill Rd, Brown Mills, NJ 08015-1799. E-mail jzhang{at}cybernet.net
Background and Purpose Extracellular nucleotides play an important role in the regulation of vascular tone and may be involved in cerebral vasospasm after subarachnoid hemorrhage. The objective of this study was to investigate the receptor subtypes for nucleotides and their mechanisms of [Ca2+]i mobilization in cerebral vasculature.
Methods Rat basilar smooth muscle cells were isolated by an enzymatic method. [Ca2+]i mobilization in freshly isolated cells was monitored using fura 2 microfluorimetry.
Result Extracellular nucleotides produced a
concentration-dependent biphasic [Ca2+]i
response, a large transient peak followed by a slowly decaying plateau.
The potency of nucleotides to raise
[Ca2+]i was ATP
S
UDP
ATP
UDP
TTP,
indicating that P2u receptors were expressed in the rat
basilar smooth muscle cells. The effect of UTP to release
Ca2+ from internal stores was reduced by pertussis toxin,
by the phospholipase C inhibitor 2-nitro-4-carboxyphenyl
N,N-diphenylcarbamate, and by the Ca2+-pump
inhibitor thapsigargin. The Ca2+ entry induced
by UTP was partially attenuated by the receptor-operated
Ca2+ channel blocker SK&F96365 and by the voltage-dependent
Ca2+ channel blocker verapamil. P2
receptor antagonists suramin and, at higher concentrations,
pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid reduced the
effect of UTP.
Conclusions The results are the first demonstration that nucleotides activate G proteincoupled P2u receptors to mobilize [Ca2+]i in rat basilar smooth muscle cells.
Key Words: rats nucleotides muscle, smooth
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