Agonist and antagonist protect sulfhydrals in the binding site of the D-1 dopamine receptor

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5220250

Sidhu, A; Kebabian, J W; Fishman, P H

An iodinated compound (/sup 125/I)-SCH 23982 (8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) has been characterized as a specific, high affinity (Kd = 0.7 nM) ligand for the D-1 dopamine receptor. The ligand binding site of the D-1 receptor in rat striatum was inactivated by N-ethylmaleimide (NEM) in a time and concentration dependent manner. The inactivation was rapid and irreversible with a 70% net loss of binding sites. Scatchard analysis of binding to NEM-treated tissue showed a decrease both in receptor number and in radioligand affinity. The remaining receptors retained their selectivity for stereoisomers of both agonist and antagonist. Receptor occupancy by either a D-1 specific agonist or antagonist protected in a dose dependent manner the binding sites from inactivation by NEM; the agonist was more effective than the antagonist. The agonist high affinity site, however, was abolished in the absence or presence of protective compound, presumably because of inactivation of the GTP-binding component of adenylate cyclase. In this regard, there was a total loss of agonist- and forskolin-stimulated adenylate cyclase activity after NEM treatment. The authors conclude that the D-1 dopamine receptor contains NEM-sensitive sulfhydral group(s) at or near the vicinity of the ligand binding site.

• Research Organization: National Institutes of Health, Bethesda, MD
• OSTI ID: 5220250
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINES
ANIMALS
ANTIMITOTIC DRUGS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BATS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL COMPOSITION
CYCLASES
DAYS LIVING RADIOISOTOPES
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
HYDROXY COMPOUNDS
IMIDES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LYASES
MAMMALS
MEMBRANE PROTEINS
NEM
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RADIOISOTOPES
RADIOSENSITIZERS
REACTION KINETICS
RECEPTORS
SYMPATHOMIMETICS
THIOLS
TIME DEPENDENCE
TRACER TECHNIQUES
VERTEBRATES