L. Cooke et Kh. Muntz, DIFFERENCES IN BETA-ADRENERGIC-RECEPTOR AGONIST AFFINITY BETWEEN CARDIAC MYOCYTES AND CORONARY ARTERIOLES IN CANINE HEART, The Journal of pharmacology and experimental therapeutics, 269(1), 1994, pp. 351-357
Beta adrenergic receptors (beta AR) are localized in several tissue co
mpartments of the heart, including cardiac myocytes, coronary arteries
and coronary arterioles, but it is unclear whether there are differen
ces between tissues in beta AR coupling to G protein. The goal of thes
e studies was to use receptor autoradiography to analyze beta receptor
agonist binding characteristics in different tissue compartments of d
og heart, including ventricular myocytes (predominantly beta-1) and co
ronary arterioles (predominantly beta-2). Frozen sections were incubat
ed in [I-125]-pindolol with the beta agonist isoproterenol in the abse
nce and presence of 0.1 mM sodium 5'-guanylylimidodiphosphate (GppNHp,
a nonhydrolyzable GTP analog) and analyzed by gamma counting or autor
adiography. Nonlinear curve-fitting analyses of ventricular section ra
dioactivity indicated that in the absence of GppNHp, the data were con
sistent with a two-site fit, with 88% of the receptors in the high-aff
inity state. In autoradiographic analyses, GppNHp displaced the agonis
t binding curve to a greater extent in arterioles (approximately 100-f
old) than in myocytes (approximately 10-fold). This suggests that beta
receptors on arterioles are more tightly coupled to G protein than ar
e beta receptors on myocytes. Thus these studies suggest that 1) beta
AR on arterioles are coupled more tightly to G protein than are beta A
R on myocytes, possibly because of differences in beta receptor subtyp
e, and 2) more beta AR are in the high-affinity state than has been re
ported previously in more traditional analyses on membrane preparation
s.