GLYCINE INCREASES THE NUMBER OF SOMATOSTATIN RECEPTORS AND SOMATOSTATIN-MEDIATED INHIBITION OF THE ADENYLATE-CYCLASE SYSTEM IN THE RAT HIPPOCAMPUS

The glycine and somatostatin (SS) neurotransmission systems in the bra in have been implicated in the function of sensory, motor, and nocicep tive pathways. To investigate a possible relationship between these tw o components, we studied the influence of glycine on the binding of I- 125-Tyr(11)-SS to its receptors and on SS-like immunoreactivity (SSLI) levels in the rat hippocampus and frontoparietal cortex, An intracere broventricular (i.c.v.) dose of 16 or 160 nmol of glycine induced an i ncrease in the total number of specific SS receptors in the hippocampu s but not in the frontoparietal cortex at 15 min following injection, with no changes in the affinity constant. This effect seems to be medi ated by inhibitory strychnine-sensitive glycine receptors since pretre atment with the antagonist strychnine (80 mu g/100 g body weight, intr avenously) abolished this response. No significant changes in SSLI con tent were detected in either brain region of glycine- and strychnine p lus glycine-treated rats as compared to control values. Since SS recep tors are coupled via guanine nucleotide-binding G proteins to the aden ylyl cyclase (AC) system, we also examined the inhibitory effects of S S and the guanine nucleotide Gpp(NH)p on AC activity in hippocampal me mbranes of control, glycine- and strychnine plus glycine-treated rats since the increase in SS receptors was observed only in this brain are a. No significant differences were observed for the forskolin (FK)-sti mulated AC enzyme activities in hippocampal membranes from all the exp erimental groups studied. In the hippocampus of the glycine- (160 nmol ) treated group, however, basal AC activity was significantly lower, a nd the capacity of SS to inhibit FK-stimulated AC activity was increas ed as compared to the control group. Pretreatment with strychnine prev ented the increase in SS-mediated inhibition of AC activity. The funct ional activity of the inhibitory guanine nucleotide-binding protein G( i) as determined by the inhibitory effect of the stable GTP analogue G pp(NH)p on FK-stimulated AC activity, was significantly higher in hipp ocampal membranes of glycine- (160 nmol) treated rats as compared to c ontrols. This suggests that the increased inhibition of AC activity by SS in the glycine-treated group may be due to the increase in G(i) ac tivity and/or the increase in the number of SS receptors observed. Alt ernatively, the greater G(i) activity may be responsible for the incre ased binding of I-125-Tyr(11)-SS to its receptors observed after glyci ne administration. Altogether, these data suggest that the hippocampal somatostatinergic system can be regulated by strychnine-sensitive gly cine receptors in the rat. (C) 1996 Wiley-Liss, Inc.