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Title: High-affinity cannabinoid binding site in brain: A possible marijuana receptor

Abstract

The mechanism by which delta{sup 9} tetrahydrocannabinol (delta{sup 9}THC), the major psychoactive component of marijuana or hashish, produces its potent psychological and physiological effects is unknown. To find receptor binding sites for THC, we designed a water-soluble analog for use as a radioligand. 5{prime}-Trimethylammonium-delta{sup 8}THC (TMA) is a positively charged analog of delta-{sup 8}THC modified on the 5{prime} carbon, a portion of the molecule not important for its psychoactivity. We have studied the binding of ({sup 3}H)-5{prime}-trimethylammonium-delta-{sup 8}THC (({sup 3}H)TMA) to rat neuronal membranes. ({sup 3}H)TMA binds saturably and reversibly to brain membranes with high affinity to apparently one class of sites. Highest binding site density occurs in brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacologial properties. Molecular sieve chromatography reveals a bimodal peak of ({sup 3}H)TMA binding activity of approximately 60,000 daltons apparent molecular weight.

Authors:
Publication Date:
Research Org.:
Johns Hopkins Univ., Baltimore, MD (USA)
OSTI Identifier:
5547702
Resource Type:
Thesis/Dissertation
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; MARIHUANA; RECEPTORS; AFFINITY; BIOCHEMICAL REACTION KINETICS; BRAIN; CELL MEMBRANES; LIGANDS; MOLECULAR WEIGHT; NERVES; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; BODY; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; HERBS; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; MAGNOLIOPHYTA; MAGNOLIOPSIDA; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; NERVOUS SYSTEM; ORGANIC COMPOUNDS; ORGANS; PLANTS; PROTEINS; REACTION KINETICS; RODENTS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Nye, J.S. High-affinity cannabinoid binding site in brain: A possible marijuana receptor. United States: N. p., 1988. Web.
Nye, J.S. High-affinity cannabinoid binding site in brain: A possible marijuana receptor. United States.
Nye, J.S. Fri . "High-affinity cannabinoid binding site in brain: A possible marijuana receptor". United States.
@article{osti_5547702,
title = {High-affinity cannabinoid binding site in brain: A possible marijuana receptor},
author = {Nye, J.S.},
abstractNote = {The mechanism by which delta{sup 9} tetrahydrocannabinol (delta{sup 9}THC), the major psychoactive component of marijuana or hashish, produces its potent psychological and physiological effects is unknown. To find receptor binding sites for THC, we designed a water-soluble analog for use as a radioligand. 5{prime}-Trimethylammonium-delta{sup 8}THC (TMA) is a positively charged analog of delta-{sup 8}THC modified on the 5{prime} carbon, a portion of the molecule not important for its psychoactivity. We have studied the binding of ({sup 3}H)-5{prime}-trimethylammonium-delta-{sup 8}THC (({sup 3}H)TMA) to rat neuronal membranes. ({sup 3}H)TMA binds saturably and reversibly to brain membranes with high affinity to apparently one class of sites. Highest binding site density occurs in brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacologial properties. Molecular sieve chromatography reveals a bimodal peak of ({sup 3}H)TMA binding activity of approximately 60,000 daltons apparent molecular weight.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 1988},
month = {Fri Jan 01 00:00:00 EST 1988}
}

Thesis/Dissertation:
Other availability
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