AJP - Heart and Circulatory Physiology, Vol 256, Issue 2 321-H327, Copyright © 1989 by American Physiological Society
Downregulation and desensitization of A1-adenosine receptors in embryonic chicken heart
J. Shryock, A. Patel, L. Belardinelli and J. Linden
Department of Medicine, College of Medicine, University of Florida, Gainesville 32610.
Downregulation of cardiac A1-adenosine receptors and desensitization of the
negative inotropic response to adenosine were examined 44 h after
pretreatment of 15-day-old chick embryos with phenylisopropyladenosine
(R-PIA) or vehicle. The number of A1-adenosine receptors, assessed by
125I-aminobenzyladenosine (125I-ABA) binding to crude cardiac membranes,
was decreased by 63% (P less than 0.001) after pretreatment of embryos with
1 mumol of R-PIA, from 16.7 +/- 2.4 to 6.2 +/- 1.4 (SD) fmol/mg protein (n
= 6). The KD of 125I-ABA binding to the remaining receptors did not differ
significantly from control (0.71 +/- 0.45 vs. 0.79 +/- 0.57 nM). A
maximally effective concentration of R-PIA (10(-5) M) decreased the
developed tension of electrically paced right ventricular (RV) muscle
strips from control embryos by 76 +/- 6% (mean +/- SD, n = 7) from its
forskolin-stimulated plateau level, whereas the developed tension of strips
from R-PIA-pretreated embryos was decreased significantly less, by 38 +/-
4% (P less than 0.001). The potency of R-PIA and the efficacy and potency
of carbachol to decrease contractile tension were not changed. The data
suggest that chronic exposure of the heart to R-PIA can produce
downregulation of A1-adenosine receptors and homologous desensitization of
the negative inotropic response to adenosine.
