NDLI: (125I)iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor.

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(125I)iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor.

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(125I)iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kahoun, J. R. Ruoho, A. E.
Description	Author Affiliation: Kahoun JR ( Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.);
Abstract	A carrier-free radioiodinated cocaine photo-affinity label, (-)-3-(125I)iodo-4-azidococaine [(125I)IACoc], has been synthesized and used as a probe for cocaine-binding proteins. Photoaffinity labeling with 0.5 nM (125I)IACoc resulted in selective derivatization of a 26-kDa polypeptide with the pharmacology of a sigma receptor in membranes derived from whole rat brain, rat liver, and human placenta. Covalent labeling of the 26-kDa polypeptide was inhibited by 1 microM haloperidol, di(2-tolyl)guanidine (DTG), 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP), dextromethorphan, and carbetapentane. Stereoselective protection of (125I)IACoc photolabeling by 3-PPP [(+)-3-PPP more potent than (-)-3-PPP] was observed. (125I)IACoc labeling of the 26-kDa polypeptide was also inhibited by 10 microM imipramine, amitriptyline, fluoxetine, benztropine, and tetrabenazine. The size of the (125I)I-ACoc-labeled proteins is consistent with the size of proteins photolabeled in guinea pig brain and liver membranes by using the sigma photolabel azido-[3H]DTG. Kinetic analysis of (125I)IACoc binding to rat liver microsomes revealed two sites with Kd values of 19 and 126 pM, respectively. The presence or absence of proteolytic inhibitors during membrane preparation did not alter the size of the photolabeled sigma receptor, indicating that the 26-kDa polypeptide was not derived from a larger protein. In summary, (125I)IACoc is a potent and highly specific photoaffinity label for the haloperidol-sensitive sigma receptor and will be useful for its biochemical and molecular characterization.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cocaine Analogs & Derivatives Haloperidol Pharmacology Receptors, Opioid Metabolism Affinity Labels Animals Binding, Competitive Biogenic Amines Biological Transport Brain Carrier Proteins Cell Membrane Chemical Synthesis Liver Microsomes, Liver Photochemistry Placenta Drug Effects Receptors, Sigma Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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