Alpha-2 Adrenoceptors Modulate the Somatostatinergic System and G Protein Levels in the Rat Hippocampus

Abstract

α₂–Adrenoceptor agonists and somatostatin (SS) exert opposite effects on the spike discharge of pyramidal and granule cells in the rat hippocampus. We studied whether clonidine, an α₂–adrenoceptor agonist, and yohimbine, an α₂-adrenoceptor antagonist, can modulate somatostatin-like immunoreactivity (SSLI) levels, binding of ¹²⁵I-Tyr¹¹-somatostatin (¹²⁵I-Tyr¹¹-SS) to its specific receptors, SS–inhibited adenylyl cyclase (AC) activity, and the guanine–nucleotide binding regulatory proteins G_i and G₀ in the rat hippocampus. Clonidine (1 mg/kg, intraperitoneally (IP) or yohimbine (5 mg/kg, IP) injected at both 10 and 16 hours before decapitation did not affect SSLI content in the hippocampus. Clonidine administration decreased the number of specific SS receptors and increased the apparent affinity in hippocampal membranes. This change in SS binding was not the result of a direct effect of clonidine on these receptors because no effect in binding was produced by high concentrations of clonidine (10⁻⁵ M) whenadded in vitro. Pretreatment with yohimbine prevented the clonidine-induced in SS binding. Yohimbine alone produced a significant increase in the number of ¹²⁵I-Tyr¹¹-SS receptors and a decrease in its apparent affinity. Clonidine decreased the ADP-ribosylation of a 41- and a 39-kDa G-protein by pertussis toxin (PTX), whereas yohimbine had no effect on the PTX-catalyzed ADP-ribosylation. No significant differences were 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 in hippocampal membranes of clonidine-treated rats, whereas yohimbine led to an opposite effect. Pretreatment with yohimbine prevented the clonidine-induced changes in AC activity. These results support the existence of a significant interaction between α₂-adrenoceptors and SS receptors in the rat hippocampus.

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