Increase of rat serum prolactin by adenosine analogs and their blockade by the methylxanthine aminophylline.

The administration of the stable adenosine analogs N6-[(R)-methyl-2-phenylethyl]adenosine (R-PIA; 0.01-1.0 mg/kg i.p.) and 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuronamide (NECA; 0.01-1.0 mg/kg i.p.) caused a dose-related (NECA) or biphasic (R-PIA) increases in rat serum prolactin. The S-isomer of PIA was inactive up to 4 mg/kg i.p. The methylxanthine aminophylline (10 and 30 mg/kg i.p.) antagonized the R-PIA- and NECA-induced elevation of prolactin suggesting an adenosine receptor-mediated effect. The dopaminergic agents L-dopa and bromocriptine antagonized the R-PIA and NECA-induced increase in serum prolactin. Haloperidol (a dopamine antagonist) and alpha-methyl-p-tyrosine (a catecholamine synthesis inhibitor) potentiated the R-PIA-induced effects. R-PIA and NECA did not displace 3H-haloperidol from rat striatal membranes nor effect in vitro prolactin release from rat anterior pituitary cells grown in culture. Based upon these findings it is postulated that R-PIA and NECA may be increasing prolactin secretion in part by inhibiting central dopamine release, although other mechanisms may also be operating.