Quantitative pharmacological analysis of 2-125I-iodomelatonin binding sites in discrete areas of the chicken brain

Journal Article · Sun Sep 01 00:00:00 EDT 1991 · Journal of Neuroscience; (United States)

OSTI ID:5031814

Siuciak, J A; Krause, D N; Dubocovich, M L ^[1]

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1. Department of Pharmacology, Northwestern University Medical School, Chicago, IL (United States)

The authors have localized and characterized 2-125I-iodomelatonin binding sites in the chicken brain using in vitro quantitative autoradiography. Binding sites were widely distributed throughout the chicken brain, predominantly in regions associated with the visual system. The specific binding of 2-125I-iodomelatonin to discrete chicken brain areas was found to be saturable, reversible, and of high affinity. The specific binding of 2-125I-iodomelatonin (75 pm) was quantitated for 40 identifiable brain regions. Eight brain regions were chosen for binding characterization and pharmacological analysis: optic tectum, Edinger-Westphal nucleus, oculomotor nucleus, nucleus rotundus, ventral supraoptic decussation, ventrolateral geniculate nucleus, neostriatum, and ectostriatum. These regions showed no rostral-caudal gradient in 2-125I-iodomelatonin specific binding, and saturation analysis revealed a single class of high-affinity sites with KD values in the range of 33-48 pM and receptor site density (Bmax) ranging from 31 to 58 fmol/mg protein. Competition experiments carried out with various indoles revealed a similar order of pharmacological affinities in these areas: melatonin greater than 6-chloromelatonin greater than methoxyluzindole greater than N-acetylserotonin greater than luzindole much greater than 5-HT greater than 5-methoxytryptamine. The affinity constants determined by quantitative autoradiography for these compounds to compete for 2-125I-iodomelatonin binding in the optic tectum correlated well with the affinities in chicken brain membranes at 25 degrees C (r = 0.966; slope = 0.845; n = 7) and 0 degree C (r = 0.946; slope = 0.379; n = 7), chicken retinal membranes (r = 0.973; slope = 0.759; n = 7), and the potency or affinity of these compounds to affect the calcium-dependent release of 3H-dopamine from the rabbit retina (r = 0.902; slope = 0.506; n = 6).

• OSTI ID: 5031814
• Journal Information: Journal of Neuroscience; (United States), Vol. 11:9; ISSN 0270-6474
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
MELATONIN
RECEPTORS
CHEMICAL COMPOSITION
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BRAIN
CALCIUM
CHICKENS
DOPAMINE
INDOLES
IODINE 125
RETINA
TISSUE DISTRIBUTION
ALKALINE EARTH METALS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIRDS
BODY
BODY AREAS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
EYES
FACE
FOWL
HEAD
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPES
KINETICS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
PYRROLES
RADIOISOTOPES
REACTION KINETICS
SENSE ORGANS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques