ALPHA-FLUOROMETHYLHISTIDINE INFLUENCES SOMATOSTATIN CONTENT, BINDING AND INHIBITION OF ADENYLYL-CYCLASE ACTIVITY IN THE RAT FRONTOPARIETAL CORTEX

Slow-wave sleep, wakefulness, locomotor activity and learning and memo ry are regulated in similar ways by somatostatin (SS) and histamine. T o clarify the possible role of endogenous histamine on the somatostati nergic system of the rat frontoparietal cortex, we studied the effect of 50 mu g of alpha-fluoromethylhistidine (alpha-FMH), a specific inhi bitor of histidine decarboxylase, administered intracerebroventricular ly (i.c.v.) at 1, 4 and 6 h, on somatostatin-like immunoreactivity (SS LI) content and the SS receptor/effector system. The histamine content in the frontoparietal cortex decreased to about 67, 60 and 72% of con trol values at 1, 4 and 6 h after alpha-FMH administration, respective ly. At 6 h after alpha-FMH injection, there was an increase in SSLI co ntent and a decrease in the number of SS receptors, with no change in the apparent affinity. No significant differences were seen for the ba sal and forskolin (FK)-stimulated adenylyl cyclase (AC) activities in the frontoparietal cortex of alpha-FMH-treated rats when compared to t he control group at all times studied. At 6 h after alpha-FMH administ ration, however, the capacity of SS to inhibit basal and FK-stimulated AC activity in the frontoparietal cortex was significantly lower than in the control group. The ability of the stable GTP analogue 5'-guany lylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC activity in frontoparietal cortex membranes was the same in the alpha-FMH-treated (6 h) and control animals. Therefore, the decreased SS-mediated inhib ition of AC activity observed in the alpha-FMH-treated rats is not due to an alteration at the guanine nucleotide-binding inhibitory protein (G(i)) level but rather may be due to the decrease in the number of S S receptors. Taken together, these data suggest that alpha-FMH influen ces the sensitivity to SS in the rat frontoparietal cortex.