Vol. 279, Issue 3, H1329-H1337, September 2000
Conditioning of 
1-adrenoceptor effect via
2-subtype on L-type
Ca2+ current in canine ventricular
myocytes
Zsolt
Nagykaldi1,
David
Kem1,3,
Ralph
Lazzara2,3, and
Bela
Szabo2,3
1 Sections of Endocrinology and 2 Cardiology,
Department of Internal Medicine, and 3 Cardiac Arrhythmia
Research Institute, University of Oklahoma Health Sciences Center
and Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104
We investigated the roles of
1- and 2-receptors (-AR) in adrenergic
enhancement of L-type Ca2+ current
(ICaL) in canine ventricular myocytes.
Isoproterenol and l-norepinephrine produced a monophasic and
a biphasic concentration-ICaL relationship (CR),
respectively. 
1-AR inhibition with prazosin and
2-AR stimulation with zinterol or
l-epinephrine shifted the CR of l-norepinephrine
leftward. Zinterol (50 nM) and l-epinephrine (10 nM), but
not prazosin, altered the biphasic CR of l-norepinephrine to
a monophasic CR. Zinterol and l-epinephrine applied after
l-norepinephrine had no effect on
ICaL. 2-AR inhibition with
ICI-118551 reduced the Emax of isoproterenol and
l-norepinephrine by 60% and abolished the augmentation of
l-norepinephrine by zinterol and l-epinephrine. Carbachol (100 nM) modestly reduced the ICaL
response to 1-AR stimulation but abolished the
enhancement via 2-AR. Zinterol augmented the enhancement
of ICaL by forskolin, IBMX, and theophylline, but not in the presence of CGP-20712A. We conclude that selective 2-AR stimulation does not increase
ICaL but enhances adenylyl cyclase activity when
stimulated via 1-AR and with forskolin. 2-AR activity preconditions adenylyl cyclase for
1-AR stimulation.
norepinephrine; carbachol; 3-isobutyl-1-methylxanthine; adenylyl
cyclase; forskolin
