Effects of iptakalim on intracellular calcium concentrations, PKA and PKC activities in rat tail artery smooth muscle cells.
- Author:
Min GAO
1
;
Yu WANG
;
Hai WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antihypertensive Agents; pharmacology; Calcium; metabolism; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases; metabolism; Diazoxide; pharmacology; Male; Muscle, Smooth, Vascular; cytology; metabolism; Pinacidil; pharmacology; Propylamines; pharmacology; Protein Kinase C; metabolism; Rats; Rats, Sprague-Dawley; Tail; blood supply
- From: Acta Pharmaceutica Sinica 2005;40(10):954-957
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the effects of iptakalim, a new structural potassium channel opener (KCO), on intracellular calcium concentration ([Ca2+]i), protein kinase C (PKC), and cAMP-dependent kinase (PKA) activities in rat tail artery smooth muscle cells (RTA-SMC), and to analyze mechanisms involved in iptakalim reversing hypertensive vascular remodeling.
METHODSRTA-SMC was cultured and passages 3-4 were used for experiment. [Ca2+] i was measured by laser scanning confocal microscope after loaded with fluorescent indicator fluo-3-acetoxymethylester, and activities of PKA and PKC were detected by commercial assay kits (the nonradioactive PepTag system) following instructions.
RESULTSCompared with baseline, [Ca2+] i reduced significantly after iptakalim- or pinacidil-treatment at concentrations of 0.1, 1 and 10 micromol x L(-1), while diazoxide caused significant decrease at concentration of 1 and 10 micromol x L(-1). After preincubation with 1 micromol x L(-1) glibenclamide, [Ca2+] i was not significantly changed when iptakalim, pinacidil or diazoxide were added at concentration of 0.1 and 1 micromol x L(-1). Activities of PKA and PKC increased significantly by 1 micromol x L(-1) iptakalim- or pinacidil-treatment, while 1 micromol x L(-1) diazoxide induced significant change in activity of PKC but not in that of PKA.
CONCLUSIONThe characteristics of iptakalim on [Ca2+] i, PKA and PKC are more or less similar to those of pinacidil. Iptakalim decreased [Ca2+] i while increased PKA and PKC activities of RTA-SMCs, which may contribute to its ability to reverse antihypertensive vascular remodeling.