Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes.
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.
Du
Yi-Mei
YM
Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030. Yimeidu@hotmail.com
Tang
Ming
M
Liu
Chang-Jin
CJ
Luo
Hong-Yan
HY
Hu
Xin-Wu
XW
D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism
D020746:Calcium Channels, L-Type; D053607:Adrenomedullin; D011493:Protein Kinase C