(3H)domperidone binding to the kidney inner medullary collecting duct dopamine-2K (DA2K) receptor

Journal Article · Thu Aug 01 00:00:00 EDT 1991 · Journal of Pharmacology and Experimental Therapeutics; (United States)

OSTI ID:5229618

Huo, T; Healy, D P ^[1]

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1. City University of New York, New York (USA)

Previous studies by the authors laboratory have indicated that inner medullary collecting ducts (IMCDs) express a novel dopamine (DA) receptor, designated DA2K, that is linked to stimulation of prostaglandin E2 production. This receptor has a distinct pharmacological profile and is similar in size, but not homologous to, the brain D2 receptor. Because the DA2-selective antagonist domperidone blocks DA-mediated stimulation of prostaglandin E2 production in IMCD cells, we utilized (3H)domperidone to study the binding characteristics of the DA2K receptor in IMCD cells. (3H)Domperidone binding was saturable and best fit to a single high density site (KD, 57.6 {plus minus} 10.5 nM; Bmax, 14.9 {plus minus} 2.7 pmol/mg protein). The specificity of (3H)domperidone binding in IMCD cells was verified by competition analysis with a variety of dopaminergic and nondopaminergic agents. Dopaminergic drugs were less potent competitors for (3H)domperidone binding in IMCD cells than previously reported for brain DA receptors, but the rank order was consistent with the labeling of a DA receptor (antagonists: domperidone greater than spiperone greater than haloperidol greater than Sch 23390 much greater than (-)-sulpiride; agonists: norapomorphine greater than fenoldopam much greater than dopamine = quinpirole), and was better correlated with the pharmacological profile for the brain D2 receptor than the brain D3 receptor. In addition, quinpirole, the most D3-selective ligand currently available, did not compete for (3H)domperidone binding in IMCD cells. These results add further support to the existence of a novel high density DA receptor, DA2K, expressed in IMCD cells.

• OSTI ID: 5229618
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (United States), Vol. 258:2; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DOPAMINE
RECEPTORS
SYMPATHOLYTICS
BIOCHEMICAL REACTION KINETICS
IN VITRO
LIGANDS
PHARMACOLOGY
RATS
SPIPERONE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUBULES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KIDNEYS
KINETICS
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques