Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling.
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.
Li
Dan
D
Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Jeonju 561-180, Korea.
Wen
Jin Fu
JF
Jin
Jing Yu
JY
Jin
Hua
H
Ann
Hai Sun
HS
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Lee
Ho Sub
HS
Cho
Kyung Woo
KW
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
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