109 COORDINATE REGULATION OF A1 AND A2 ADENOSINE RECEPTOR IN CULTURED NEUROBLASTOMA AND LYMPHOBLASTOID CELLS

Abstract

In a variety of tissues, both A1 and A2 receptors have been demonstrated; in several instances they facilitate opposing physiological effects. We have found both A1 and A2 receptors on the surface of cultured murine neuroblastoma (NB) cells. A1 receptors predominate in B and A2 receptors in T lymphoblastoid (LB) cells. Many studies have shown upregulation of A1 receptors by methylxanthines (MXs), while a few have suggested that carbamazepine (CBZ) acts as an A1 antagonist. The present investigation demonstrates that A2 receptors are also upregulated in NB cells and in T LB cells either by acute (16 hr) or chronic (1-3 week) exposure to MX. The effects were time and dose dependent, and are stimulated as well by CPT, a presumed A1 antagonist. Binding studies show an increase in number of receptors, but no change in affinity. The physiological balance between A1/A2 effects is thus primarily a function of the concentration of agonist present in these isolated cell systems. There is also evidence to suggest that drugs may shift the balance of A1/A2 actions in clinical situations. We show that ethanol acutely increases the sensitivity of A2 receptors; chronic ethanol diminishes it. Chronic effects are not reflected in increased binding sites. Contrary to published reports, CBZ (a widely used anticonvulsant) facilitates actions of ADO at A2 receptors, but inhibits Al response. Supported in part by the Medical Research Council of Canada.