K+ACh channel activation with carbachol increases atrial ANP release.
Although it has been known that atrial natriuretic peptide (ANP) release is regulated through muscarinic acetylcholine receptors (mAChR), the mechanism by which this neurotransmitter regulates atrial ANP release is largely unknown. This study tested the hypothesis that K(+)(ACh) channels mediate the action of mAChR on atrial myocyte ANP release. Experiments were performed in perfused beating rabbit atria. Carbachol (CCh), an agonist of cardiac mAChR, increased atrial myocyte ANP release concomitantly with a decrease in stroke volume and intra-atrial pulse pressure in a concentration-dependent manner. Isoproterenol, a beta-adrenoceptor agonist, decreased ANP release concomitantly with an increase in cAMP and mechanical dynamics. In the presence of isoproterenol, the CCh-induced increase in ANP release and decrease in cAMP efflux levels and mechanical dynamics were able to be repeated. The CCh-induced changes were blocked by selective M(2) mAChR antagonists. Tertiapin, a selective G-protein-gated K(+)(ACh) channel blocker, attenuated the CCh-induced increase in ANP release and decrease in mechanical dynamics in a concentration-dependent manner, but without a significant effect on the CCh-induced decrease in cAMP efflux levels. The CCh-induced changes in ANP release and atrial dynamics were inhibited in the atria from pertussis toxin-pretreated rabbits. These findings demonstrate that G-protein-gated K(+)(ACh) channels regulate atrial myocyte ANP release. The present study also shows that mAChR and adrenoceptors have opposing roles in the regulation of ANP release.
Xu
Dong Yuan
DY
Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Jeonju, South Korea.
Wen
Jin Fu
JF
Quan
He Xiu
HX
Zhou
Guang Hai
GH
Kim
Sun Young
SY
Park
Sung Hun
SH
Kim
Sung Zoo
SZ
Lee
Ho Sub
HS
Cho
Kyung Woo
KW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001514:Bee Venoms / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006321:Heart / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D011817:Rabbits; D011863:Radioimmunoassay; D043585:Receptor, Muscarinic M2 / Q000819:agonists / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D001514:Bee Venoms; D020746:Calcium Channels, L-Type; D018721:Muscarinic Agonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; C029738:tertiapin; D009320:Atrial Natriuretic Factor; D002217:Carbachol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol