Regulation of dopamine D2 receptors in a novel cell line (SUP1)
- Univ. of Pennsylvania School of Medicine, Philadelphia (USA)
A prolactin-secreting cell line, SUP1, has been established from rat pituitary tumor 7315a. In radioligand binding experiments, the D2 receptor antagonist (S)-(-)-3-{sup 125}I iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2- pyrrolidinyl)methyl)benzamide ({sup 125}I IBZM) labeled a single class of sites in homogenates of SUP1 cells (Kd = 0.6 nM; Bmax = 45 fmol/mg of protein). The sites displayed a pharmacological profile consistent with that of D2 receptors. Inhibition of the binding of {sup 125}I IBZM by dopamine was sensitive to GTP, suggesting that D2 receptors in SUP1 cells are coupled to guanine nucleotide-binding protein(s). In the presence of isobutylmethylxanthine, dopamine decreased the level of cAMP accumulation in SUP1 cells. Dopamine also inhibited prolactin secretion from SUP1 cells. Both the inhibition of cAMP accumulation and the inhibition of prolactin secretion were blocked by D2 receptor antagonists, suggesting that these effects of dopamine were mediated by an interaction with D2 receptors. The regulation of D2 receptors in SUP1 cells by D2 receptor agonists was investigated. Exposure of SUP1 cells to dopamine or to the D2 receptor agonist N-propylnorapomorphine led to increased expression of D2 receptors, with no change in the affinity of the receptors for {sup 125}I IBZM. An increase in the density of D2 receptors in SUP1 cells was evident within 7 hr of exposure to dopamine. Spiroperidol, a D2 receptor antagonist, blocked the effect of dopamine on receptor density. These results suggest that exposure of D2 receptors in SUP1 cells to agonists leads to an up-regulation of D2 receptors. Dopamine retained the ability to inhibit cAMP accumulation in SUP1 cells exposed to dopamine for 24 hr, suggesting that D2 receptors in SUP1 cells are not desensitized by prolonged exposure to agonist.
- OSTI ID:
- 5672183
- Journal Information:
- Molecular Pharmacology; (USA), Vol. 39:4; ISSN 0026-895X
- Country of Publication:
- United States
- Language:
- English
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DOPAMINE
RECEPTORS
ENZYME INHIBITORS
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AMP
IODINE 125
LTH
RATS
TRACER TECHNIQUES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
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ELECTRON CAPTURE RADIOISOTOPES
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HORMONES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
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IODINE ISOTOPES
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MEMBRANE PROTEINS
NEUROREGULATORS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHENOLS
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REACTION KINETICS
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SYMPATHOMIMETICS
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