HISTAMINE H-1-RECEPTORS MODULATE SOMATOSTATIN RECEPTORS COUPLED TO THE INHIBITION OF ADENYLYL-CYCLASE IN THE RAT FRONTOPARIETAL CORTEX

Since exogenous histamine has been previously shown to increase the so matostatin (SS) receptor-effector system in the rat frontoparietal cor tex and both histamine H-1-receptor agonists and SS modulate higher ne rvous activity and have anticonvulsive properties, it was of interest to determine the participation of the H-1-histaminergic system in this response. The intracerebroventricular (i.c.v.) administration of the specific histamine H-1-receptor agonist 2-pyridylethylamine (PEA) (10 mu g) to rats 2 h before decapitation increased the number of SS recep tors (599 +/- 40 vs 401 +/- 31 femtomoles/mg protein, p < 0.01) and de creased their apparent affinity for SS (0.41 +/- 0.03 vs 0.26 +/- 0.02 nM, p < 0.01) in rat frontoparietal cortical membranes. No significan t differences were seen for the basal and forskolin (FK)-stimulated ad enylyl cyclase (AC) activities in the frontoparietal cortex of PEA-tre ated rats when compared to the control group. In the PEA group, howeve r, the capacity of SS (10(-4) M) to inhibit basal and FK (10(-5) M)-st imulated AC activity in frontoparietal cortical membranes was signific antly higher than in the control group (34 +/- 1% vs 20 +/- 2%, p < 0. 001). The ability of low concentrations of the stable GTP analogue 5'- guanylylimidodiphosphate [Gpp(NH)p] to inhibit FK-stimulated AC activi ty in frontoparietal cortical membranes was similar in the PEA-treated and control animals. These results suggest that the increased SS medi ated inhibition of AC activity in the frontoparietal cortex of PEA-tre ated rats may be due to the increase of the number of SS receptors ind uced by PEA. Pretreatment with the H-1-receptor antagonist mepyramine (30 mg/kg, intraperitoneally (IP) prevented the PEA-induced changes in SS binding and SS-mediated inhibition of AC activity. Mepyramine (30 mg/kg, IP) alone had no observable effect on the somatostatinergic sys tem. The in vitro addition of PEA or mepyramine to frontoparietal cort ical membranes obtained from untreated rats did not affect the SS bind ing parameters. Altogether, these results suggest that the H-1-histami nergic system modulates the somatostatinergic system in the rat fronto parietal cortex. (C) 1997 Elsevier Science Inc.