Angiotensin II stimulation of Ca2+-channel current in vascular smooth muscle cells is inhibited by lavendustin-A and LY-294002

• Published in: Pflügers Archiv Vol. 437; no. 3; pp. 317 - 323
• Main Authors: Seki, T, Yokoshiki, H, Sunagawa, M, Nakamura, M, Sperelakis, N
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01-02-1999
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Angiotensin II - pharmacology; Animals; Aorta; Calcium Channels - drug effects; Calcium Channels - physiology; Cell Line; Cells; Chromones - pharmacology; Electric Conductivity; Enzyme Inhibitors - pharmacology; Kinases; Kinetics; Morpholines - pharmacology; Phenols - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinase Inhibitors; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Proteins; Rats
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004240050785

Angiotensin II (AngII) is coupled to several important intracellular signaling pathways, and increases intracellular Ca2+. In vascular smooth muscle (VSM) cells, AngII is known to activate enzymes such as tyrosine protein kinase (Tyr-PK), phospholipase C (PLC), protein kinase C (PKC), and phophatidylinositol-3-kinase (PI-3-K). A non-receptor Tyr-PK, pp60(c-src), and PKC have been reported to stimulate the Ca2+ channels in VSM cells. However, less is known about AngII action on the voltage-gated Ca2+ channels. The Ca2+-channel currents of a cultured rat aortic smooth muscle cell line, A7r5, were recorded using whole-cell voltage clamp. Application of 50 nM AngII significantly increased the amplitude of Ba2+ currents through the voltage-gated Ca2+ channels (IBa) by 34. 5+/-9.1% (n=10) within 1 min. In the presence of lavendustin-A (5 microM), a selective inhibitor of Tyr-PK, AngII failed to stimulate IBa (n=5). AngII stimulation of IBa was also prevented by (5 microM) LY-294002, an inhibitor of PI-3-K (n=5). In contrast, H-7 (30 microM), an inhibitor of PKC, did not prevent the effect of AngII on IBa (n=6). These results suggest that AngII may stimulate the Ca2+ channels of VSM cells through Tyr-PK and PI-3-K under conditions that probably exclude participation of PK-C.