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The effect of phenylephrine on inositol 1,4,5-trisphosphate levels in vascular smooth muscle measured using a protein
1Division of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Abstract:
This study utilizes a protein binding assay system to evaluate agonist-induced changes in inositol 1,4,5-trisphosphate (IP3) in rat aorta. Phenylephrine induced a rapid transient increase in IP3 content of rat aorta which was concentration dependent and blocked by prazosin. The concentration response curve to IP3 formation was shifted to the right of the concentration-response curve for contraction in normal calcium-containing buffer but was close to that obtained in calcium-free medium. This suggests that although IP3 may play an important role in mediating release of intracellular Ca2+, other factors (e.g. Ca2(+)-influx) may be involved in determining the magnitude of vascular smooth muscle contraction in Ca2(+)-containing solutions. Both 8-bromo cyclic GMP and sodium nitroprusside significantly attenuated the phenylephrine-induced IP3 formation. Removal of the endothelium did not alter the generation of IP3.