Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

In-vitro characterization and regulation of multiple brain serotonin receptors

Thesis/Dissertation ·
OSTI ID:5566070
In this thesis a potent hallucinogen, {sup 3}H-({plus minus})-4-bromo-2,5-dimethoxyphenylisopropylamine ({sup 3}H-DOB) was developed as a radiolabel for the serotonin receptor subtype designated 5-HT{sub 2}. The specific binding of {sup 3}H-DOB to a particulate fraction prepared from homogenates of rat brain frontal cortex displayed saturability with a maximum capacity (B{sub max}) of 17.9 fmoles/mg protein and high affinity with an equilibrium dissociation constant (K{sub D}) of 0.41 nM. The distribution of specific {sup 3}H-DOB binding in nine brain regions correlated closely with the distribution of 5-HT{sub 2} receptors specifically labelled by {sup 3}H-ketanserin (a serotonin antagonists selective for the receptor subtype). The B{sub max} of {sup 3}H-DOB labeled sites was 4% of the B{sub max} of {sup 3}H-ketanserin labeled sites. Competition experiments revealed a distinct 5-HT{sub 2} receptor pharmacology in that serotonergic antagonists competed with similar affinities for {sup 3}H-DOB as for {sup 3}H-ketanserin. Serotonergic agonists competed for specific {sup 3}H-DOB binding with 10-100 fold higher affinity than for {sup 3}H-ketanserin labeled 5-HT{sub 2} receptors. {sup 3}H-DOB specific binding was potently inhibited by the guanine nucleotide analogs GppNHp and GTPgammaS (IC{sub 50's} of 42 and 21 nM respectively) while the adenine nucleotides had no effect. Thus, it appears that {sup 3}H-DOB specific binding displays the pharmacological characteristics of a 5-HT{sub 2} receptor and that it is coupled to a guanine nucleotide regulatory protein.
Research Organization:
Albany Medical Coll., NY (USA)
OSTI ID:
5566070
Country of Publication:
United States
Language:
English

Similar Records

Autroadiographic characterization of sup 125 I-labeled 2,5-dimethoxy-4-iodophenylisopropylamine (DOI): A phenylisopropylamine derivative labeling both 5HT sub 2 and 5HT sub 1c receptors
Conference · Sun Feb 25 23:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States) · OSTI ID:5489268
( sup 3 H)-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and ( sup 3 H) ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor
Journal Article · Wed Oct 31 23:00:00 EST 1990 · Molecular Pharmacology; (USA) · OSTI ID:6324950
4-( sup 125 I)iodo-(2,5-dimethoxy)phenylisopropylamine and ( sup 3 H)ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: Evidence for multiple states and not multiple 5HT2 receptor subtypes
Journal Article · Wed Oct 31 23:00:00 EST 1990 · Molecular Pharmacology; (USA) · OSTI ID:6073422

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENINES
AMINES
ANIMALS
ANTIMETABOLITES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CEREBRAL CORTEX
CEREBRUM
DRUGS
GUANINE
HALLUCINOGENS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
INDOLES
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
PURINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES