Exogenous histamine increases the somatostatin receptor/effector system in the rat frontoparietal cortex

Abstract

The present study examined the effects of histamine on somatostatin-like immunoreactivity levels, binding of 125I-[Tyr 11]somatostatin to its 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 μg or 1 μg of histamine induced an increase in the number of specific 125I-[Tyr 11]somatostatin receptors (590 ± 22 vs 358 ± 12 fmol/mg protein, P < 0.001 and 455 ± 20 vs 342 ± 21 fmol/mg protein, P < 0.01, respectively) together 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 increase in tracer binding was not due to a direct effect of histamine on the 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 adenylyl cyclase activity in frontoparietal cortex membranes of histamine-treated rats as compared with the control group. In rats treated with 10 μg of histamine, however, somatostatin caused a significantly greater inhibition of basal and forskolin-stimulated adenylyl cyclase activity as compared to the control group (33 ± 4% vs 19 ± 1% inhibition, P < 0.05 and 31 ± 1% vs 21 ± 3% inhibition, P < 0.05, respectively). The functional activity of the G i protein, as measured by the capacity of the stable GTP analogue 5′guanylylimidodiphosphate [Gpp(NH)p] to inhibit forskolin-stimulated adenylyl cyclase activity, was not altered by 10 μg of histamine in frontoparietal cortex membranes. Therefore, the observed increase in somatostatin inhibition of adenylyl cyclase activity in the frontoparietal cortex from rats treated with this histamine dose may be caused by the increase in the number of somatostatin receptors. To determine whether the above-mentioned changes 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 H 2 receptor antagonists mepyramine and cimetidine, respectively, which were administered simultaneously. This pretreatment prevented the histamine-induced changes in the somatostatin receptor/effector system in the frontoparietal cortex. In conclusion, these results suggest that the somatostatinergic system present in the frontoparietal cortex can be regulated by histamine and that this regulation may be implicated in some of the behavioural effects of histamine and somatostatin.