Autoradiographic characterization of (+-)-1-(2,5-dimethoxy-4-( sup 125 I) iodophenyl)-2-aminopropane (( sup 125 I)DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain
- National Institute on Drug Abuse Addiction Research Center, Baltimore, MD (USA)
The 5-HT2 (serotonin) receptor has traditionally been labeled with antagonist radioligands such as (3H)ketanserin and (3H)spiperone, which label both agonist high-affinity (guanyl nucleotide-sensitive) and agonist low-affinity (guanyl nucleotide-insensitive) states of this receptor. The hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is an agonist which labels the high-affinity guanyl nucleotide-sensitive state of brain 5-HT2 receptors selectively. In the present study, conditions for autoradiographic visualization of (+/-)-(125I)DOI-labeled 5-HT2 receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanyl nucleotide sensitivity and anatomical distribution. In slide-mounted rat brain sections (+/-)-(125I)DOI binding was saturable, of high affinity (KD approximately 4 nM) and displayed a pharmacologic profile typical of 5-HT2 receptors. Consistent with coupling of 5-HT2 receptors in the high-affinity state to a guanyl nucleotide regulatory protein, (125I)DOI binding was inhibited by guanyl nucleotides but not by adenosine triphosphate. Patterns of autoradiographic distribution of (125I)DOI binding to 5-HT2 receptors were similar to those seen with (3H)ketanserin- and (125I)-lysergic acid diethylamide-labeled 5-HT2 receptors. However, the density of 5-HT2 receptors labeled by the agonist (125I)DOI was markedly lower (30-50%) than that labeled by the antagonist (3H)ketanserin. High densities of (125I)DOI labeling were present in olfactory bulb, anterior regions of cerebral cortex (layer IV), claustrum, caudate putamen, globus pallidus, ventral pallidum, islands of Calleja, mammillary nuclei and inferior olive. Binding in hippocampus, thalamus and hypothalamus was generally sparse.
- OSTI ID:
- 6324457
- Journal Information:
- Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 255:2; ISSN 0022-3565; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL COMPOSITION
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HALLUCINOGENS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SERINE
SEROTONIN
SPIPERONE
SYMPATHOMIMETICS
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES