Mm. Zhao et al., REGULATION OF ALPHA(1)-ADRENERGIC, BETA(1)-ADRENERGIC, AND BETA(2)-ADRENERGIC RECEPTORS IN RAT-HEART BY NOREPINEPHRINE, American journal of physiology. Heart and circulatory physiology, 40(5), 1996, pp. 1762-1768
Previous studies suggest that the desensitization and downregulation o
f beta(1)-adrenergic receptors (beta(1)-AR) in the failing heart are t
he result of the elevated plasma catecholamine levels associated with
this disease. To examine norepinephrine (NE)-induced regulation of car
diac adrenergic receptors, rats were infused with l-NE (200 mu g . kg(
-1). h(-1) for 7 days) or vehicle (0.001 N HCl) by implantation of osm
otic minipumps. The technique of coverslip autoradiography was used to
quantify alpha(1)-adrenergic receptors (alpha(1)-AR), beta(1)-AR, and
beta(2)-AR in different tissue compartments of rat hearts. For measur
ement of beta-AR binding, sections were incubated with 70 pM [I-125]io
docyanopindolol (ICYP) alone or in the presence of 5 mu M dl-propranol
ol or 5 x 10(-7) M CGP-20712A (a beta(1)-antagonist) and then set up f
or autoradiography. [H-s]prazosin (1 nM) with or without phentolamine
was used to study alpha-AR binding. Chronic infusion of NE induced a g
reater downregulation of beta(2)-AR compared with beta(1)-AR in all re
gions studied, including atrial and ventricular myocytes, coronary art
erioles, and connective tissue. An 18% loss of beta(1)-AR was seen onl
y in atrial myocytes; beta(1)-AR density actually increased 28% in ven
tricular myocytes following NE infusion. There was a 15% decrease in a
lpha(1)-AR in ventricular myocytes, whereas no change in alpha(1)-AR d
ensity was seen in myocardial arterioles. Our study demonstrates that
beta(2)-AR are more susceptible to NE-induced downregulation than beta
(1)-AR. Thus other mechanisms mag be involved in the selective downreg
ulation of beta(1)-AR in certain forms of heart failure.