Inhibition of cyclic AMP accumulation by α2-adrenoceptors in the rat cerebral cortex

Abstract

The effects of α 2-adrenoceptor agonist and antagonists on the accumulation of cyclic AMP were examined in rat cerebral cortex slices. Norepinephrine (10 −4 M) caused a 123±11% increase in the cyclic AMP concentration in the cortical slices, which was greater than the increase (89±7% increase) caused by isoproterenol (10 −4 M) alone. However, the cyclic AMP response to norepinephrine was completely inhibited by propranolol (10 −4 M), a β-adrenoceptor antagonist. Yohimbine (10 −7 −10 −5 M), an α 2-adrenoceptor antagonist, intensified the cyclic AMP response to norepinephrine by 30%, whereas, clonidine, an α 2-adrenoceptor agonist, decreased the response. Treatment with reserpine (3.0 mg/kg) reduced the density of [ 3H]p-aminoclonidine binding sites (B max, 93.8±18.4 fmol/mg protein) compared to the density in non-treated rats (154.4±33.5 fmol/mg protein). The potentiating effect of yohimbine and the inhibitory effect of clonidine on the cyclic AMP response to norepinephrine were also reduced. These results suggest that α 2-adrenoceptors regulate the accumulation of cyclic AMP in the rat cerebral cortex in an inhibitory fashion. The results also suggest that the accumulation is mediated through β-adrenoceptors and that this response is intensified by α 1-adrenoceptor stimulation.