title: Inhibition of beta-adrenergic signaling by intracellular AMP is independent of cell-surface adenosine receptors in rat cardiac cells.
abstract: We report a novel action of intracellular adenosine monophosphate (AMP) to inhibit beta-adrenergic signaling in isolated rat ventricular myocytes. Extracellular application of adenosine or AMP suppressed isoproterenol (Iso)-induced prolongation of action potential duration (APD). This effect was completely abolished by an A(1)-receptor antagonist, DPCPX. Intracellular application of AMP, but not adenosine, attenuated Iso-induced APD prolongation. Iso-induced increases in the L-type Ca(2+) current (I(Ca,L)) were also inhibited by intracellular AMP. These inhibitory effects were not affected by either DPCPX or glibenclamide. In vitro, AMP directly inhibited PKA activity via binding to its regulatory subunit. These results suggest that intracellular AMP attenuates beta-adrenergic signaling by directly inhibiting PKA activity, independently of A(1)-purinergic receptor.
authors: Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Japan.
authors: Kazuyoshi
authors: K
authors: Ogura
authors: Junichiro
authors: J
authors: Miake
authors: Norihito
authors: N
authors: Sasaki
authors: Chisato
authors: C
authors: Iwai
authors: Udin
authors: U
authors: Bahrudin
authors: Peili
authors: P
authors: Li
authors: Masaru
authors: M
authors: Kato
authors: Kazuhiko
authors: K
authors: Iitsuka
authors: Yutaka
authors: Y
authors: Hirota
authors: Toshiya
authors: T
authors: Koshida
authors: Yasutaka
authors: Y
authors: Yamamoto
authors: Yoshiaki
authors: Y
authors: Inoue
authors: Akio
authors: A
authors: Yano
authors: Masamitsu
authors: M
authors: Adachi
authors: Osamu
authors: O
authors: Igawa
authors: Yasutaka
authors: Y
authors: Kurata
authors: Takayuki
authors: T
authors: Morisaki
authors: Goshi
authors: G
authors: Shiota
authors: Yasuaki
authors: Y
authors: Shirayoshi
authors: Ninomiya
authors: N
authors: Haruaki
authors: Ichiro
authors: I
authors: Hisatome
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
chemical_list: D011943:Receptors, Adrenergic, beta; D018047:Receptors, Purinergic P1; D000249:Adenosine Monophosphate; D000241:Adenosine