Regulation of 1, 1, and 2-adrenergic receptors in rat heart by
norepinephrine.
Zhao, Mingming, Herbert K. Hagler, Kathryn H. Muntz.
Department of Cell Biology and Neuroscience, Department of
Pathology, University of Texas Southwestern Medical Center at Dallas,
Dallas, TX 75235-9039
APStracts 3:0293H, 1996.
Previous studies have suggested that the desensitization and down
-regulation of 1-adrenergic receptors (1AR) in the failing heart are
the result of the elevated plasma catecholamine levels associated
with this disease. To examine norepinephrine (NE)-induced regulation
of cardiac adrenergic receptors, rats were infused with l-NE (200
[mu]g/kg/hr for 7 days) or vehicle (0.001N HCl) by implantation of
osmotic mini-pumps. The technique of coverslip autoradiography was
used to quantify [alpha]1-adrenergic receptors ( 1AR), 1AR and 2AR in
different tissue compartments of rat hearts. For measurement of AR
binding, sections were incubated with 70 pM [125I]iodocyanopindolol
(ICYP) alone or in the presence of 5 [mu]M d,l-propranolol or 5 x 10
-7 M CGP 20712A (a 1-antagonist) and then set up for autoradiography.
[3H]prazosin (1 nM) with or without phentolamine was used to study AR
binding. Chronic infusion of NE induced a greater down-regulation of
2AR when compared to 1AR in all regions studied, including atrial and
ventricular myocytes, coronary arterioles and connective tissue. An
18% loss of 1AR was seen only in atrial myocytes; 1AR density
actually increased 28% in ventricular myocytes following NE infusion.
There was a 15% decrease in 1AR in ventricular myocytes, while no
change in 1AR density was seen in myocardial arterioles. Our study
demonstrates that 2AR are more susceptible to NE-induced down
-regulation than 1AR. Thus, other mechanisms may be involved in the
selective down-regulation of 1AR in certain forms of heart failure.
Received 1 August 1994; accepted in final form 29 February 1996.
APS Manuscript Number H683-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996