Adenosine and divalent cation effects on S-91 melanoma adenylate cyclase

Adenosine inhibits S-91 melanoma membrane adenylate cyclase. This inhibition is observed with all activators tested; α-melanocyte-stimulating hormone, [norleucine⁴]α-melanocyte-stimulating hormone, prostaglandin-E₂, and fluoride ion. This inhibition is also observed with the ribose modified adenosine analog adenine-9-β-d-arabinofuranoside. However, "R" site (stringent for the ribose moiety) analogs such as 2-chloroadenosine and 6-methyladenosine were without effect. Addition of manganous ion (Mn²⁺), a potent activator of adenylate cyclase, markedly enhances the inhibition by adenosine. The nucleoside specificity, Mn²⁺ requirement, and lack of reversal by the potent R-site antagonist, 3-isobutyl-1-methylxanthine, suggest that the S-91 melanoma membrane adenylate cyclase system contains only P-type (stringent for purine moiety) receptor sites.