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Cyclic GMP‐mediated inhibition of L‐type Ca 2+ channel activity by human natriuretic peptide in rabbit heart cells
Author(s) -
Tohse Noritsugu,
Nakaya Haruaki,
Kanno Youji Takeda Morio
Publication year - 1995
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.1476-5381.1995.tb13316.x
Subject(s) - atrial natriuretic peptide , medicine , chemistry , endocrinology , patch clamp , phosphodiesterase , activator (genetics) , intracellular , second messenger system , phosphodiesterase inhibitor , biophysics , protein kinase a , electrophysiology , kinase , biochemistry , biology , receptor , enzyme
1 Effects of atrial natriuretic peptide (ANP) on the L‐type Ca 2+ channels were examined in rabbit isolated ventricular cells by use of whole‐cell and cell‐attached configurations of the patch clamp methods. ANP produced a concentration‐dependent decrease (10–100 n m ) in amplitude of a basal Ca 2+ channel current. 2 The inactive ANP (methionine‐oxidized ANP, 30 n m ) failed to decrease the current. 3 8‐Bromo‐cyclic GMP (300 μ m ), a potent activator of cyclic GMP‐dependent protein kinase (PKG), produced the same effects on the basal Ca 2+ channel current as those produced by ANP. The cyclic GMP‐induced inhibition of the Ca 2+ channel current was still evoked in the presence of 1‐isobutyl‐3‐methyl‐xanthine, an inhibitor of phosphodiesterase. ANP failed to produce inhibition of the Ca 2+ channel current in the presence of 8‐bromo‐cyclic GMP. 4 In the single channel recording, ANP and 8‐bromo‐cyclic GMP also inhibited the activities of the L‐type Ca 2+ channels. Both agents decreased the open probability (NP 0 ) without affecting the unit amplitude. 5 The present results suggest that ANP inhibits the cardiac L‐type Ca 2+ channel activity through the intracellular production of cyclic GMP and then activation of PKG.