Coupling mechanisms of alpha 2-adrenoceptors.

Activation of adrenoceptors of the alpha 2-subtype can cause an inhibitory or an excitatory response, depending on the cellular system affected. At the plasma membrane, where the extracellular signal is transduced via the alpha 2-adrenoceptor into an intracellular signal, only one transduction process has clearly been established until now by studies in various cellular systems, namely the inhibition of adenylate cyclase. The enzyme inhibition, which is caused by activation of alpha 2-adrenoceptors, is mediated by the inhibitory guanine nucleotide-binding regulatory component (Ni). This component serves as coupler between the activated alpha 2-adrenoceptor and the adenylate cyclase. Selective inactivation of Ni by pertussis toxin not only impairs the alpha 2-adrenoceptor-mediated adenylate cyclase inhibition but also the overall cellular response caused by activation of the receptors. It is suggested that Ni and the adenylate cyclase inhibition mediated by this regulatory protein is the major cellular transduction process following interaction of agonists with alpha 2-adrenoceptors.