title: Protein kinase-dependent and Ca(2+)-independent cAMP inhibition of ANP release in beating rabbit atria.
abstract: Regulation of atrial release of atrial natriuretic peptide (ANP) is coupled to changes in atrial dynamics. However, the mechanism by which mechanical stretch controls myocytic ANP release must be defined. The purpose of this study was to define the mechanism by which cAMP controls myocytic ANP release in perfused, beating rabbit atria. The cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX) inhibited myocytic ANP release. The activation of adenylyl cyclase with forskolin inhibited ANP release, which was a function of an increase in cAMP production. Inhibitors for L-type Ca(2+) channels and protein kinase A (PKA) attenuated a minor portion of the forskolin-induced inhibition of ANP release. Gö-6976 and KN-62, which are specific inhibitors for protein kinase C-alpha and Ca(2+)/calmodulin kinase, respectively, failed to modulate forskolin-induced inhibition of ANP release. The nonspecific protein kinase inhibitor staurosporine blocked forskolin-induced inhibition of ANP release in a dose-dependent manner. Staurosporine but not nifedipine shifted the relationship between cAMP and ANP release. Inhibitors for L-type Ca(2+) channels and PKA and staurosporine blocked forskolin-induced accentuation of atrial dynamics. These results suggest that cAMP inhibits atrial myocytic release of ANP via protein kinase-dependent and L-type Ca(2+)-channel-dependent and -independent signaling pathways.
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Jeonju 561-180, Korea.
authors.forename: Xun
authors.initials: X
authors.lastname: Cui
authors.forename: Jin Fu
authors.initials: JF
authors.lastname: Wen
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Jin
authors.forename: Wen Xie
authors.initials: WX
authors.lastname: Xu
authors.forename: Sung Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Cho
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016275:Atrial Function / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002227:Carbazoles; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D005576:Colforsin; C057416:KT 5720; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D019311:Staurosporine; D009543:Nifedipine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine