An endogenous ligand for the sigma opioid binding site.
It had been suggested that phencyclidine (PCP) and sigma opioids exert their similar psychotomimetic effects through a common receptor. Recently, however, there have been several reports demonstrating significant differences between the binding of PCP and SKF 10,047, a sigma opioid agonist, which suggests that there may be distinct PCP and sigma opioid receptors. If these differences in binding represent different receptors, then there may be different endogenous ligands for each receptor. Using porcine brains, which have already been used to isolate and purify an endogenous ligand for the PCP receptor, another factor has been isolated that inhibited the binding of [3H]-(+)SKF 10,047 and not the binding of [3H]-PCP. This factor appears to be a peptide or protein because incubation of the active fraction with pronase, a nonspecific peptidase, eliminated the ability of the porcine fractions to inhibit the binding of [3H]-(+)SKF 10,047. These findings suggest the existence of an endogenous ligand for sigma opioid receptors, which is different from the previously identified endogenous ligand for PCP receptors.
Contreras
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Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
DiMaggio
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O'Donohue
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism; D011957:Receptors, Opioid / Q000302:isolation & purification / Q000378:metabolism*; D017480:Receptors, sigma; D013552:Swine
D004723:Endorphins; D008024:Ligands; D011957:Receptors, Opioid; D017480:Receptors, sigma; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine