Molecular Regulatory Mechanism of D2 Dopamine Receptor in the Bovine Striatum
There is considerable evidence for the existence of multiple types of dopamine receptor in the brain. D1 have been defined by their ability to elicit an increase in adenylate cyclase activity while D2 receptors do not activate this enzyme (1). Recently, in experiments using homogenates of the intermediate lobe of the rat pituitary gland, it has been shown that stimulation of the D2 decreases the responsiveness of the beta-adrenoceptor by reducing adenylate cyclase activity, and that guanine nucleotides are obligatory for receptor-mediated stimulation and for inhibition of adenylate cyclase (2). However, although it has been demonstrated that guanine nucleotides decrease the affinity of agonists but not antagonists for the brain D2 receptor and that stimulation of the D2 receptor results in a reduction in cAMP efflux from rat striatal slices, the inhibition of adenylate cyclase activity mediated by the D2 receptor has not been directly deter-mined (3–6). Islet-activating protein (IAP), a pertussis toxin, inhibits the inhibition of adenylate cyclase activity mediated by alpha2-adrenergic, cholinergic, and opiate receptors in neuroblas-toma x glioma hybrid cells, and modulates the binding affinities of these receptors, presumably as a result of ADP-ribosylation of one of the subunits of the inhibitory guanine nucleotide regulatory protein, designated Ni (3–6). Thus, we attempted to determine whether IAP modulates the GTP-sensitive adenylate cyclase activity and the binding affinity of the bovine striatal D2 receptor associated with ADP-ribosylation of a subunit of Ni.
KeywordsAdenylate Cyclase Guanine Nucleotide Pertussis Toxin Adenylate Cyclase Activity Spiperone Binding
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