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Effects of inhibitors of protein kinase C and Na + /H + exchange on α 1 ‐adrenoceptor‐mediated inotropic responses in the rat left ventricular papillary muscle
Author(s) -
Otani Hitomi,
Otani Hajime,
Uriu Toshiko,
Hara Mitsuyoshi,
Inoue Masafumi,
Omori Kyoko,
Cragoe Edward J.,
Inagaki Chiyoko
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15783.x
Subject(s) - staurosporine , amiloride , protein kinase c , medicine , endocrinology , chemistry , stimulation , papillary muscle , inotrope , protein kinase a , kinase , biology , biochemistry , sodium , organic chemistry
1 α 1 ‐Adrenoceptor stimulation of rat left ventricular papillary muscle produced a triphasic inotropic response: an initial transient positive inotropic effect (PIE) followed by a transient negative inotropic effect (NIE) and a sustained PIE. 2 The protein kinase C inhibitor, staurosporine, at concentrations ranging from 30 n m to 100 n m inhibited the sustained PIE, but had no significant effect on the transient PIE and NIE. 3 H‐7, 1‐(5‐isoquinoline sulphonyl)‐2‐methylpiperazine, a less specific inhibitor of protein kinase C than staurosporine, at a concentration of 100 μ m inhibited both the transient NIE and the sustained PIE without affecting the transient PIE. 4 Amiloride, an inhibitor of Na + /H + exchange, at concentrations ranging from 0.1 m m to 1 m m inhibited the sustained PIE and, at higher concentrations, also inhibited the transient NIE. 5 An amiloride analogue, 5‐(N‐methyl‐N‐isobutyl)amiloride (MIBA), inhibited only the sustained PIE with an IC 50 of 0.3 μ m which is approximately two orders of magnitude lower than amiloride. 6 The receptor‐linked stimulation of Na + /H + exchange through protein kinase C activation may be a mechanism for α 1 ‐adrenoceptor‐mediated sustained PIE.