Stimulation of G‐protein coupled receptors in vascular smooth muscle cells induces tyrosine kinase dependent increases in calcium without tyrosine phosphorylation of phospholipase C γ‐1

摘要

>It is often believed that increases in intracellular Ca2+ ([Ca2+]_i) resulting from stimulation of G-protein coupled receptors in vascular smooth muscle cells (VSMC) require activation of the β1 isoform of phospholipase C (PLC). However, recent studies showed that rat aortic VSMC do not express PLC β-1 and that stimulation with angiotensin-II induces tyrosine kinase dependent increases in [Ca2+]_i and tyrosine phosphorylation of PLC γ-1. Whether this pathway is activated by other vasoactive agents that stimulate G-protein coupled receptors is unknown. Here, we show that A10 VSMC express PLC β-2, PLC β-3, PLC δ-1, and PLC γ-1. The cells also expressed Gα_q/11. However, neither PLC β-1 nor PLC β-4 was detected. Stimulation with angiotensin-II, vasopressin, serotonin, or endothelin induced tyrosine kinase dependent increases in [Ca2+]_i. However, tyrosine phosphorylation of PLC γ-1 did not occur. In contrast, stimulation with platelet derived growth factor increased [Ca2+]_i and tyrosine phosphorylation of PLC γ-1. The results show that tyrosine phosphorylation of PLC γ-1 is not required for tyrosine kinase dependent increases in [Ca2+]_i resulting from stimulation of diverse G-protein coupled receptors in VSMC.