Function and Mechanism of the Interaction of GTP-Binding Proteins with α2-Adrenoceptors in the Brain
Multiple subtypes of adrenoceptors including αl-, α2-, β1- and β2-adrenoceptors have been found in the central nervous system (CNS) (1, 2). Stimulation of α2-adrenoceprtors causes inhibition of adenylate cyclase activity (3), and inhibition of noradrenaline (NA) release from central and peripheral noradrenergic nerve terminals (4). Clonidine exerts hypotensive and sedative effects by its acting on α2-adrenoceptors in the brain (5). Pertussis toxin, isletactivating protein (IAP), suppresses the inhibition of adenylate cyclase activity mediated by inhibitory receptors such as α2-adrenoceptor, D2-dopamine receptor, muscarinic acetylcholine receptor and opiate receptor, and modulates the agonist-binding affinities of these receptors as result of ADP-ribosylation of α-subunit of inhibitory GTP-binding protein, Gi (6). To gain insight into the functional roles, the molecular mechanism and aging in coupling of α2-adrenoceptor with Gi in the CNS, we investigated influences of clonidine and IAP on locomotor activity in rats, NA release from brain slices and adenylate cyclase activity in brain membranes.
KeywordsAdenylate Cyclase Cholera Toxin Pertussis Toxin Adenylate Cyclase Activity Noradrenaline Release
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