Regulation of dopamine D2 receptors by sodium and pH

Journal Article · Mon Apr 01 04:00:00 EST 1991 · Molecular Pharmacology; (USA)

OSTI ID:5527532

Neve, K A ^[1]

---

1. VA Medical Center, Portland, OR (USA)

The role of Na+ and H+ in the regulation of D2 receptor affinity for ligands was studied to determine the molecular mechanisms of this phenomenon. The potency of substituted benzamide derivatives and agonists at D2 receptors depended on the concentration of Na+ and H+, whereas the potency of other antagonists was relatively unaltered by changes in pH or Na+ concentration. The potency of agonists was generally decreased in the presence of NaCl or lowered pH. For example, in the absence of sodium the affinity of D2 receptors for dopamine was decreased 17-fold by lowering of the pH from 8.0 to pH 6.8. Addition of NaCl caused 2-4-fold decreases in affinity for most agonists. The affinity of the receptors for two substituted benzamide derivatives, on the other hand, was reduced 6-44-fold by elevated concentrations of H+ but was enhanced 7-24-fold in the presence of Na+. The regulation by H+ of the potency of dopamine was selective for D2 receptors, because binding of dopamine to neostriatal D1 receptors was unaffected by changes in pH. Decreasing of the pH from 8.0 or 7.3 to 6.8 facilitated the dissociation of the substituted benzamide ligand {sup 125}I epidepride from D2 receptors but inhibited dissociation of {sup 3}H spiperone. Furthermore, the presence of NaCl or lowered pH slowed inactivation of D2 receptors by N-ethylmaleimide. Together, these data suggest that the conformation of D2 receptors is regulated by both Na+ and H+. The affinity of D2 receptors for agonists and substituted benzamide antagonists varies according to the conformational state of the receptors, whereas other antagonists bind to both forms with approximately equal potency. Amiloride is a compound that interacts with many sodium-binding macromolecules.

• OSTI ID: 5527532
• Journal Information: Molecular Pharmacology; (USA), Journal Name: Molecular Pharmacology; (USA) Vol. 39:4; ISSN 0026-895X; ISSN MOPMA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALI METAL COMPOUNDS
ALKALI METALS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BARYONS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DOPAMINE
DRUGS
ELEMENTARY PARTICLES
ELEMENTS
FERMIONS
HADRONS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
METALS
MICE
NEUROREGULATORS
NUCLEONS
ORGANIC COMPOUNDS
PH VALUE
PHENOLS
POLYPHENOLS
PROTEINS
PROTONS
RADIOASSAY
REACTION KINETICS
RECEPTORS
RODENTS
SODIUM
SODIUM COMPOUNDS
SPIPERONE
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES