cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

• 영문명: cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Li-qun Peng Ping Li Qiu-li Zhang Lan Hong Li-ping Liu Xun Cui Bai-ri Cui
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제20권 제1호, 9~14쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2016.01.01

영문 초록

Adenosine 3 ,5 -cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na⁺-K⁺-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 μmol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabainincreased atrial dynamics was blocked by KB-R7943 (3.0 μmol/L), an inhibitor for reverse mode of Na⁺-Ca²⁺ exchangers (NCX), but did not by L-type Ca²⁺ channel blocker nifedipine (1.0 μmol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 μmol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 μmol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 μmol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 μmol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

키워드

Adenosine 3 ,5 -cyclic monophosphate (cAMP) Endothelin-1 (ET-1) Mitogen-activated protein kinase (MAPK) Ouabain