5′-Deoxy-5′-methylthioadenosine: A nucleoside which differentiates between adenosine receptor types

Abstract

The activities of an endogenous nucleoside, 5′-deoxy-5′-methylthioadenosine (MTA), on adenosine sensitive sites such as adenosine a 1 and A 2 receptors and the P-site, as well as on purine nucleoside transport, have been studied. This nucleoside competitively antagonized the A 2 receptor-mediated stimulation of neuroblastoma adenylate cyclase, produced a GTP-dependent and 8- p-sulfophenyltheophylline-sensitive inhibition of adenylate cyclase activity in rat cerebellar membranes, and decreased the spontaneous contractile activity of isolated segments of rabbit jejunum. MTA was neither active at the P-site nor did it diminish the binding of [ 3Hnitrobenzylthioinosine, a nucleoside transport inhibitor. We conclude that (a) MTA is an agonist at the adenosine A 1 receptor but an antagonist at the A 2 receptor, and (b) the adenosine receptor which causes relaxation of rabbit jejunum is not a neuroblastoma-type A 2 receptor which activates adenylate cyclase.