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Angiotensin-receptor signaling in cultured vascular smooth muscle cells

作者:Juline Smith · 发表于:American Journal of Physiology-Renal Physiology · 年份:1986 · DOI:10.1152/ajprenal.1986.250.5.f759 · 被引用次数:86 · 研究领域:Renin-Angiotensin System Studies、Protein Kinase Regulation and GTPase Signaling、Ion Transport and Channel Regulation

Functional receptors for angiotensin II (ANG II) are present in smooth muscle cells cultured from rat aorta. These cells are especially suitable for investigating transmembrane signaling events, since ANG II-receptor function is consistently expressed for many population doublings in culture. Cytoplasmic free Ca, measured with quin 2 or fura-2, transiently increases after receptor stimulation. ANG II releases Ca that is sequestered intracellularly, since the removal of extracellular Ca does not prevent the hormone from increasing intracellular free Ca. Angiotensin provokes both polyphosphoinositide hydrolysis and phosphatidate-phosphoinositide synthesis. Purified inositol trisphosphate (IP3) releases Ca from a nonmitochondrial organelle, presumably the sarcoplasmic reticulum or a specialized region therein. IP3 probably opens an intracellular Ca channel by a ligand-binding reaction rather than a metabolic reaction. The accumulation of IP3 in intact cells in response to ANG II seems fast enough to cause Ca mobilization. ANG II increases a fast and a slow component of 45Ca2+ efflux from the intact cells. The rapid stimulation of Ca2+ efflux from the cell via a Na-Ca antiporter probably accounts at least in part for the short duration of the increase in cytoplasmic free Ca elicited by angiotensin. ANG II has no effect on a fast component of 45Ca2+ influx but does increase a slow component of 45Ca2+ influx; that increase would help to sustain the elevation in free Ca and the refi...