Evidence for an endogenous peptide ligand for the phencyclidine receptor |
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Authors: | R Quirion D A DiMaggio E D French P C Contreras J Shiloach C B Pert H Everist A Pert T L O'Donohue |
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Affiliation: | 1. Experimental Therapeutics Branch, NINCDS, NIH, Building 10, Room 5C 207, Bethesda, MD 20205, USA;2. Douglas Hospital Research Centre, Verdun, Quebec, Canada H4H 1R3;3. Clinical Neuroscience Branch, NIMH, NIH, Bethesda, MD 20205, USA;4. Maryland Psychiatric Research Center, University of MD, Baltimore, MD 21218, USA;5. Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20205, USA;6. National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20205, USA;7. Department of Medicine, Howard University, Washington, D.C. 20059, USA |
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Abstract: | Porcine brain contained an active factor that competed with [3H]-phencyclidine (PCP) for binding to rat brain membranes. On reverse phase high pressure liquid chromatography, the active material eluted between 38-42% acetonitrile. Gel filtration chromatography of the factor predicted a molecular weight of approximately 3000 daltons. The endogenous substance appeared to be selective for PCP receptors as it did not interact with either benzodiazepine, neurotensin, nor with mu, delta, or kappa opioid receptors. The active material showed a heterogenous distribution in brain, with highest concentrations found in hippocampus and cortex. It is likely to be a small peptide since various proteases eliminated or markedly reduced the potency of the compound in a [3H]-PCP binding assay. The material also possessed PCP-like activity in two bioassays. Like PCP, it induced contralateral rotational behavior after unilateral intranigral injection and depressed spontaneous cell activity after iontophoretic micropressure application in hippocampus and cerebral cortex. Thus, this small peptide is likely to be an endogenous ligand for the PCP receptor. |
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Keywords: | PCP Angel dust Brain Schizophrenia Behavior Neuropeptide |
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