Cyclic adenosine 3',5'-monophosphate in rat cerebral cortical slices: effects of methoxamine and clonidine

In incubated slices of cerebral cortex from Sprague-Dawley rats, methoxamine and clonidine have no effect on basal levels of cyclic AMP. Methoxamine effectively inhibits the noradrenaline-stimulated formation of cyclic AMP. The inhibitory constant for methoxamine was 12.6 mumol/l. In the presence of 100 mumol/l adenosine, methoxamine does not inhibit the activity of noradrenaline, but is capable to activate alpha-adrenergic receptors leading to enhanced formation of cyclic AMP. The mechanism by which adenosine alters adrenergic receptors to become methoxamine-sensitive is not known. Clonidine inhibits the effect of noradrenaline alone or in combination with adenosine on the cyclic-AMP-generating system. It does not, as reported earlier, enhance the activity of submaximal concentrations of the beta-adrenergic agonist isoproterenol. These data do not support the concept of adrenergic receptors which require both, alpha- and beta-stimulation for maximal activation of adenylate cyclase.