Effect of adenosine receptor agonists and antagonists on transport of adenosine in bovine heart microvascular endothelial cells.

Abstract

Adenosine produces a variety of effects through binding to adenosine receptors. It has been found that the adenosine receptors: A1, A2A, A2B and A3, are involved in the cardioprotection and cerebroprotection, in regulation of sleep and pain, in immunological and inflammatory responses, in respiratory regulation and in kidney function, the processes known to be regulated by adenosine . Since the attempts to activate Ado receptors for clinical benefits through pharmacologically elevated adenosine concentrations were not successful , a number of synthetic adenosine receptor agonists and antagonists were developed to manipulate Ado receptor function . Although adenosine receptor agonists/antagonists binding was studied in detail, relatively little is known about other biochemical effects of these compounds. In our experiments a number of agonists and antagonists of adenosine receptors (A1, A2, A3) was studied for effects on adenosine transport and adenosine release in bovine heart microvascular endothelial cells (BHMEC). In the BHMEC cells, in which the coronary responses to adenosine agonists in many cases seem to be endothelium mediated 7,8 , adenosine receptor agonists, particularly of A3 and A1 type, inhibited adenosine influx (IC50 0.766 μM) (Table 1). The most potent inhibition was observed with I-ABA, ABA, CHA, and N6-phenyladenosine. Contrary, the A2 receptor