Downregulation and desensitization of A1-adenosine receptors in embryonic chicken heart.

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.