EFFECT OF SULPIRIDE ON SOMATOSTATIN RECEPTORS, SOMATOSTATIN-LIKE IMMUNOREACTIVITY AND MODULATION OF ADENYLYL-CYCLASE ACTIVITY IN THE RAT-BRAIN

The present study investigates the effects of the administration of an intracerebroventricular (i.c.v.) dose of 500 mu g/rat of the neurolep tic (-) sulpiride on somatostatin-like immunoreactivity (SSLI) levels, I-125-Tyr(11)-SS binding to its specific receptors, SS-modulated aden ylyl cyclase (AC) activity and the pertussis toxin (PTX) substrates me asured by toxin-catalysed ADP ribosylation of the alpha-subunits from G-proteins. (-) Sulpiride significantly decreased the SSLI levels in t he frontoparietal cortex at 30 min but was without effect on the SSLI concentration in the striatum. This decrease had disappeared within 24 hr. The administration of (-) sulpiride produced a significant increas e in the number of I-125-Tyr(11)-SS receptors and a significant reduct ion in their affinity at 30 min after injection in the striatum withou t affecting the frontoparietal cortex. The effects of the (-) sulpirid e injection had disappeared after 24 hr. This change in SS binding was not due to a direct effect of (-) sulpiride on these receptors since no effect on binding was produced by high concentrations of (-) sulpir ide (10(-5) M) when added in vitro. No significant differences were se en in either brain region for the basal or the forskolin (FK)-stimulat ed AC enzyme activities in the control and (-) sulpiride groups. In th e (-) sulpiride group, the capacity of SS to inhibit FK-stimulated AC in the frontoparietal cortex was significantly higher than in the cont rol group with no significant difference in the striatum. These result s correlate with the increase of a 41 kDa PTX substrate, presumably th e alpha-i-subunit of Gi substrates in frontoparietal cortex and striat um 30 min after (-) sulpiride administration with respect to the corre sponding controls.