Inhibition of beta-adrenergic signaling by intracellular AMP is independent of cell-surface adenosine receptors in rat cardiac cells.
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.
Ogura
Kazuyoshi
K
Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Japan.
Miake
Junichiro
J
Sasaki
Norihito
N
Iwai
Chisato
C
Bahrudin
Udin
U
Li
Peili
P
Kato
Masaru
M
Iitsuka
Kazuhiko
K
Hirota
Yutaka
Y
Koshida
Toshiya
T
Yamamoto
Yasutaka
Y
Inoue
Yoshiaki
Y
Yano
Akio
A
Adachi
Masamitsu
M
Igawa
Osamu
O
Kurata
Yasutaka
Y
Morisaki
Takayuki
T
Shiota
Goshi
G
Shirayoshi
Yasuaki
Y
Haruaki
Ninomiya
N
Hisatome
Ichiro
I
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
D011943:Receptors, Adrenergic, beta; D018047:Receptors, Purinergic P1; D000249:Adenosine Monophosphate; D000241:Adenosine