EXOGENOUS HISTAMINE INCREASES THE SOMATOSTATIN RECEPTOR-EFFECTOR SYSTEM IN THE RAT FRONTOPARIETAL CORTEX

The present study examined the effects of histamine on somatostatin-li ke immunoreactivity levels, binding of I-125[Tyr(11)]somatostatin to i ts specific receptors, somatostatin inhibition of basal and forskolin- stimulated adenylyl cyclase activity and inhibitory guanine-nucleotide binding protein (G(i)) function in the rat frontoparietal cortex. An intracerebroventricular (i.c.v.) dose of 10 mu g or 1 mu g of histamin e induced an increase in the number of specific I-125-[Tyr(11)]somatos tatin receptors (590 +/- 22 vs 358 +/- 12 fmol/mg protein, P < 0.001 a nd 455 +/- 20 vs 342 +/- 21 fmol/mg protein, P < 0.01, respectively) t ogether with a decrease in their apparent affinity (0.76 +/- 0.04 vs 0 .39 +/- 0.02 nM, P < 0.001 and 0.60 +/- 0.03 vs 0.39 +/- 0.05 nM, P < 0.01, respectively) in rat frontoparietal cortex membranes. This incre ase in tracer binding was not due to a direct effect of histamine on t he somatostatin receptors since no change in binding was produced when histamine was added directly to the incubation medium. No significant differences were seen for either the basal or forskolin-stimulated ad enylyl cyclase activity in frontoparietal cortex membranes of histamin e-treated rats as compared with the control group. In rats treated wit h 10 mu g of histamine, however, somatostatin caused a significantly g reater inhibition of basal and forskolin-stimulated adenylyl cyclase a ctivity as compared to the control group (33 +/- 4% vs 19 +/- 1% inhib ition, P < 0.05 and 31 +/- 1% vs 21 +/- 3% inhibition, P < 0.05, respe ctively). The functional activity of the G(i) protein, as measured by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate [G pp(NH)p] to inhibit forskolin-stimulated adenylyl cyclase activity, wa s not altered by 10 mu g of histamine in frontoparietal cortex membran es. Therefore, the observed increase in somatostatin inhibition of ade nylyl cyclase activity in the frontoparietal cortex from rats treated with this histamine dose may be caused by the increase in the number o f somatostatin receptors. To determine whether the above-mentioned cha nges are related to histamine binding to its specific receptor sites H -1 and H-2, one group of rats were pretreated with the histamine H-1 a nd H-2 receptor antagonists mepyramine and cimetidine, respectively, w hich were administered simultaneously. This pretreatment prevented the histamine-induced changes in the somatostatin receptor-effector syste m in the frontoparietal cortex. In conclusion, these results suggest t hat the somatostatinergic system present in the frontoparietal cortex can be regulated by histamine and that this regulation may be implicat ed in some of the behavioural effects of histamine and somatostatin.