REGULATION OF A(1) ADENOSINE RECEPTORS BY AMIODARONE AND ELECTRICAL-STIMULATION IN RAT MYOCARDIAL-CELLS IN-VITRO

The effects of conditions that either increase or decrease heart rate on the pharmacological properties of adenosine receptors in cultured r at myocytes were examined. Levels of A(1) adenosine receptors, followi ng prolonged treatment with electrical stimulation (ES) or the antiarr hythmic drug amiodarone, were determined using radioligand binding wit h the specific A(1) receptor antagonist [H-3]1,3-dipropyl-8-cyclopenty lxanthine (CPX). The effects of lowering temperature were also explore d. Exposure to amiodarone for 4 days reduced the density of A(1) recep tors by 19% (from 24.7 +/- 0.4 to 20.09 +/- 0.3 fmol/dish) and inhibit ed the rate of contraction by 60% (from 188 +/- 16 to 76 +/- 30 beats/ min), without changing the receptor affinity, protein content, creatin e kinase (CK) activity or cell number. Electrical stimulation at 25 de grees C elevated the density of A(1) adenosine receptors by 185% (from 4.1 +/- 0.4 to 11.69 +/- 2.1 fmol/dish). Four days of reduced tempera ture (from 37 degrees C to either 30 or 25 degrees C) lowered the dens ity of A(1) adenosine receptors by 69 or 86%, respectively (from 24.1 +/- 1.2 to 7.4 +/- 0.4 or 3.4 +/- 0.3 fmol/dish), with no significant change in the receptor affinity, activity of CK, or lactate dehydrogen ase (LDH), protein content or cell number. The observed up-and down-re gulation of A(1) adenosine receptors in primary myocyte cultures in re sponse to conditions that exogenously alter the rate of contraction, i s indicative of the role of adenosine receptors in adaptation of heart cells to stress. (C) 1997 Elsevier Science Inc.