Selective decrease in the affinity of D2 dopamine receptor for agonist induced by islet-activating protein, pertussis toxin, associated with ADP-ribosylation of the specific membrane protein of bovine striatum

Abstract

When the crude synaptic membrane preparations from bovine striatum were treated with islet-activating protein (IAP), one of the pertussis toxins, a protein with a molecular weight of about 40,000 was ADP-ribosylated. In parallel with this ADP-ribosylation, there was a decrease in D2 dopamine receptor affinity for agonist, while the affinity for antagonist remained unaltered. Addition of GTP to nontreated membranes also resulted in a decrease in the affinity of D2 receptor for agonist, and there was no further reduction of affinity for agonist with addition of GTP to the IAP-treated membranes. As IAP specifically acts on the guanine nucleotide regulatory protein which mediates the inhibition of adenylate cyclase activity (Ni), our findings indicate a possible molecular interaction between the brain D2 dopamine receptor and Ni.