MDL-101,562 BLOCKS THE STIMULATORY EFFECTS OF BOMBESIN AND GASTRIN-RELEASING PEPTIDE ON HYPOTHALAMIC DOPAMINERGIC-NEURONS

The effects of central administration of bombesin, gastrin-releasing p eptide (GRP) and a putative bombesin/GRP receptor antagonist [Phe(8) P si[CH2S]Leu(9)]litorin (MDL-101,562) were determined on the activities of hypothalamic tuberoinfundibular and periventricular-hypophysial do paminergic neurons in male rats. Dopaminergic neuronal activity was es timated by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence and the intermediate lobe of the poster ior pituitary which contain terminals of these neurons. Intracerebrove ntricular injections of bombesin and GRP increased DOPAC concentration s in both the median eminence and intermediate lobe. MDL-101,562 had n o effect on median eminence or intermediate lobe DOPAC concentrations per se, but blocked the stimulatory actions of bombesin and GRP on DOP AC concentrations in these regions. These results suggest that MDL-101 ,562 may be a useful pharmacologic tool in the study of the central ac tions of bombesin and related peptides.