title: Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling.
abstract: Changes in cyclic nucleotide production and atrial dynamics have been known to modulate atrial natriuretic peptide (ANP) release. Although cardiac atrium expresses histamine receptors and contains histamine, the role of histamine in the regulation of ANP release has to be defined. The purpose of the present study was to define the effect of histamine on the regulation of ANP release in perfused beating rabbit atria. Histamine decreased ANP release concomitantly with increases in cAMP efflux and atrial dynamics in a concentration-dependent manner. Histamine-induced decrease in ANP release was a function of an increase in cAMP production. Blockade of histamine H2 receptor with cimetidine but not of H1 receptor with triprolidine abolished the responses of histamine. Cell-permeable cAMP analog, 8-Br-cAMP, mimicked the effects of histamine, and the responses were dose-dependent and blocked by a protein kinase A (PKA)-selective inhibitor, KT5720. Nifedipine failed to modulate histamine-induced decrease in ANP release. Protein kinase nonselective inhibitor staurosporine blocked histamine-induced changes in a concentration-dependent manner. KT5720 and RP-adenosine 3',5'-cyclic monophosphorothioate, another PKA-selective inhibitor, attenuated histamine-induced changes. These results suggest that histamine decreases atrial ANP release by H2 receptor-cAMP signaling via PKA-dependent and -independent pathways.
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Jeonju 561-180, Korea.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Jin Fu
authors.initials: JF
authors.lastname: Wen
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Jin
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Hai Sun
authors.initials: HS
authors.lastname: Ann
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: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D011817:Rabbits; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011970:Receptors, Histamine H2; D014665:Vasodilator Agents; D006632:Histamine; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases