ALPHA-2-ADRENOCEPTORS MODULATE THE SOMATOSTATINERGIC SYSTEM AND G-PROTEIN LEVELS IN THE RAT HIPPOCAMPUS

alpha(2)-Adrenoceptor agonists and somatostatin (SS) exert opposite ef fects on the spike discharge of pyramidal and granule cells in the rat hippocampus. We studied whether clonidine, an alpha(2)-adrenoceptor a gonist, and yohimbine, an alpha(2)-adrenoceptor antagonist, can modula te somatostatinlike immunoreactivity (SSLI) levels, binding of I-125-T yr(11)-somatostatin (I-125-Tyr(11)-SS) to its specific receptors, SS-i nhibited adenylyl cyclase (AC) activity, and the guanine-nucleotide bi nding regulatory proteins G(i) and G(o) in the rat hippocampus. Clonid ine (1 mg/kg, intraperitoneally (IP) or yohimbine (5 mg/kg, IP) inject ed at both 10 and 16 hours before decapitation did not affect SSLI con tent in the hippocampus. Clonidine administration decreased the number of specific SS receptors and increased the apparent affinity in hippo campal membranes. This change in SS binding was not the result of a di rect effect of clonidine on these receptors because no effect in bindi ng was produced by high concentrations of clonidine (10(-5) M) when ad ded in,vitro. Pretreatment with yohimbine prevented the clonidine-indu ced in SS binding. Yohimbine alone produced a significant increase in the number of I-125-Tyr(11)-SS receptors and a decrease in its apparen t affinity. Clonidine decreased the ADP-ribosylation of a 41- and a 39 -kDa G-protein by pertussis toxin (PTX), whereas yohimbine had no effe ct on the PTX-catalyzed ADP-ribosylation. No significant differences w ere seen for the basal or for the forskolin (FK)-stimulated AC enzyme activities in the control, clonidine- and/or yohimbine-treated groups. Somatostatin caused a significantly lower inhibition in AC activity i n hippocampal membranes of clonidine-treated rats, whereas yohimbine l ed to an opposite effect. Pretreatment with yohimbine prevented the cl onidine-induced changes in AC activity. These results support the exis tence of a significant interaction between alpha(2)-adrenoceptors and SS receptors in the rat hippocampus.