Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes.
- Author:
Yi-Mei DU
1
;
Ming TANG
;
Chang-Jin LIU
;
Hong-Yan LUO
;
Xin-Wu HU
Author Information
1. Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030. Yimeidu@hotmail.com
- Publication Type:Journal Article
- MeSH:
Adrenomedullin;
pharmacology;
Animals;
Calcium Channels, L-Type;
metabolism;
Guinea Pigs;
Heart Ventricles;
cytology;
Myocytes, Cardiac;
drug effects;
metabolism;
Patch-Clamp Techniques;
Protein Kinase C;
metabolism
- From:
Acta Physiologica Sinica
2002;54(6):479-484
- CountryChina
- Language:English
-
Abstract:
The effects of adrenomedullin (ADM) on the L-type calcium currents (I(Ca,L)) and the mechanism of the signal transduction process were studied. Enzymatically isolated guinea-pig ventricular myocytes were used to measure ICa,L with whole-cell patch-clamp techniques. ADM at the concentrations of 1-100 nmol/L decreased ICa,L in a dose-dependent manner (P<0.05). ADM22-52) (100 nmol/L), a specific ADM-receptor antagonist, completely abolished the ADM-induced inhibition of ICa,L. Pretreatment of the cells with H-89 (10 micromol/L), a specific PKA inhibitor, did not attenuate the effects of ADM. Intracellular application of 10 micromol/L PKC19-36), a specific PKC inhibitor, prevented the ADM-induced inhibition of the ICa,L, while the specific PKC activator PMA could mimic the effects of ADM on the ICa,L. PMA (1 micromol/L) decreased the ICa,L by 32.26+/-4.20%(P<0.05). These findings indicate that ADM can inhibit the ICa,L in guinea-pig ventricular myocytes, and the inhibition is mediated by the specific ADM-receptor and an activation of protein kinase C.
