DIRECT EFFECT OF ADENOSINE ON PROLACTIN SECRETION AT THE LEVEL OF THESINGLE-RAT LACTOTROPH - INVOLVEMENT OF PERTUSSIS-TOXIN-SENSITIVE AND PERTUSSIS-TOXIN-INSENSITIVE TRANSDUCING MECHANISMS

We studied the effect of adenosine on prolactin secretion by the anter ior pituitary, and the transduction mechanisms whereby the purine exer ts its action. Adenosine inhibited prolactin release in basal and in v asoactive intestinal peptide (VIP)- or TRH-stimulated conditions. Pert ussis toxin pretreatment reduced the inhibition of VIP-stimulated prol actin secretion which was induced by adenosine, while it completely ab olished the effect of the purine on TRH-evoked prolactin release. In m embrane preparations of anterior pituitary cells, adenosine reduced th e adenylate cyclase activity stimulated by VIP. Such an inhibition was not blocked by pertussis toxin pretreatment. Furthermore, the purine reduced TRH-stimulated inositol phosphate production in cultured anter ior pituitary cells, an effect that was reversed by pretreatment with pertussis toxin. In addition, the nucleoside did not significantly aff ect the TRH-induced rise in intracellular calcium. In conclusion, our data show that adenosine inhibits prolactin secretion, acting on purin ergic receptors coupled to the adenylate cyclase enzyme and phospholip ase C. The effect of the nucleoside on adenylate cyclase seems to be a chieved either by the involvement of an adenosine receptor coupled to the catalytic subunit of the enzyme via a pertussis toxin-sensitive G protein, or by the activation of a site directly coupled to the cataly tic subunit of the adenylate cyclase (the P site). Its effect on phosp holipase C seems to be mediated by a purinergic receptor coupled to th e intracellular effector via a pertussis toxin-sensitive G protein.