Differentiation of 5-hydroxytryptamine2 receptor subtypes using sup 125 I-R-(-)2,5-dimethoxy-4-iodo-phenylisopropylamine and sup 3 H-ketanserin

Journal Article · Sun Oct 01 00:00:00 EDT 1989 · Journal of Neuroscience; (USA)

OSTI ID:5189188

McKenna, D J; Peroutka, S J ^[1]

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1. Stanford Univ., CA (USA)

The radioligand binding characteristics of 125I-R-(-)4-iodo-2,5-dimethoxyphenylisopropylamine (125I-R-(-)DOI) and 3H-ketanserin were compared in rat and bovine cortical membranes. In rat cortex, 125I-R-(-)DOI labels a relatively low density of binding sites (Bmax = 2.5 +/- 0.2 pmol/gm tissue) with high affinity (KD = 0.63 +/- 0.09 nM). In bovine cortex, specific binding of 125I-R-(-)DOI represents less than 20% of total binding at radioligand concentrations above 0.6 nM, and, therefore, the data cannot be analyzed adequately by Scatchard transformation. By contrast, 3H-ketanserin displays saturable, specific high-affinity binding in both rat cortex (KD = 1.0 +/- 0.1 nM; Bmax = 11 +/- 0.4 pmol/gm tissue) and bovine cortex (KD = 1.2 +/- 0.2 nM; Bmax = 5.3 +/- 0.4 pmol/gm tissue). Ki values for 30 drugs were determined for 125I-R-(-)DOI-labeled sites in rat cortex and 3H-ketanserin-labeled sites in bovine cortex. 5-Hydroxytryptamine (5-HT) displays 250-fold higher selectivity for the 125I-R-(-)DOI-labeled sites (Ki = 3.0 +/- 0.7 nM) than for the 3H-ketanserin-labeled sites (Ki = 750 +/- 50 nM). Structural congeners of R-(-)DOI display 80- to 160-fold higher affinity for the 125I-R-(-)DOI binding site than for the 3H-ketanserin-labeled binding site. d-LSD and putative 5-HT2 antagonists are approximately equipotent at both sites. Significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and putative 5-HT2A sites labeled previously by 77Br-R-(-)DOB (r = 0.93, p less than 0.01), putative 5-HT2B sites labeled by 3H-ketanserin in bovine cortex (r = 0.63, p less than 0.01), and 5-HT1C binding sites that have been characterized by other investigators (r = 0.78, p less than 0.01). No significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and 5-HT1A, 5-HT1B, 5-HT1D, or 5-HT3 sites, as determined by previous investigators.

• OSTI ID: 5189188
• Journal Information: Journal of Neuroscience; (USA), Vol. 9:10; ISSN 0270-6474
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HALLUCINOGENS
BIOCHEMICAL REACTION KINETICS
SEROTONIN
RECEPTORS
BIOCHEMISTRY
CATTLE
CELL MEMBRANES
CEREBRAL CORTEX
DOSE-RESPONSE RELATIONSHIPS
IODINE 125
RATS
TRACER TECHNIQUES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BODY
BRAIN
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CEREBRUM
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RODENTS
RUMINANTS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques