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Titolo:
ABSENCE OF D-2S DOPAMINE-RECEPTOR IN THE PROLACTIN-SECRETING MMQ PITUITARY CLONE - CHARACTERIZATION OF A WILD D-2L RECEPTOR-COUPLED TO NATIVE TRANSDUCTION MECHANISMS
Autore:
VENTRA C; MEUCCI O; GRIMALDI M; SCORZIELLO A; PORCELLINI A; SCHETTINI G;
Indirizzi:
UNIV NAPLES,FAC MED & CHIRURG,DIPARTIMENTO NEUROSCI & COMUNICAZ INTERUMANA,SEZ FARMACOL I-80131 NAPLES ITALY UNIV NAPLES,FAC MED & CHIRURG 2,DIPARTIMENTO NEUROSCI & COMUNICAZ INTERUMANA I-80131 NAPLES ITALY UNIV NAPLES,FAC MED & CHIRURG 2,DIPARTIMENTO BIOL & PATOL CELLULARE &MOLEC I-80131 NAPLES ITALY
Titolo Testata:
Journal of molecular endocrinology
fascicolo: 3, volume: 14, anno: 1995,
pagine: 375 - 389
SICI:
0952-5041(1995)14:3<375:AODDIT>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT LACTOTROPH CELLS; POTASSIUM CHANNELS; ADENYLATE-CYCLASE; SOMATOSTATIN INHIBITION; MOLECULAR-BIOLOGY; D2 RECEPTOR; G-PROTEIN; LINE; EXPRESSION; TUMOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
C. Ventra et al., "ABSENCE OF D-2S DOPAMINE-RECEPTOR IN THE PROLACTIN-SECRETING MMQ PITUITARY CLONE - CHARACTERIZATION OF A WILD D-2L RECEPTOR-COUPLED TO NATIVE TRANSDUCTION MECHANISMS", Journal of molecular endocrinology, 14(3), 1995, pp. 375-389

Abstract

We used the PCR amplification technique in an attempt to characterizefurther the dopamine D-2L receptor expressed in the prolactin-secreting pituitary MMQ cell clone, derived from the prolactin- and ACTH-secreting Buffalo rat 7315a pituitary tumour. By semiquantitative PCR amplification we were unable to detect the mRNA encoding the D-2S receptorisoform, which derives from the well-known process of alternative splicing, producing two D-2 receptor subtypes (D-2L and D-2S) in such tissues as the anterior pituitary and the corpus striatum. Although the pharmacology of the D-2 receptor has been established in many studies on both native receptors and transfected receptor isoforms, because of the lack of tissues naturally expressing only one receptor isoform, MMQ cells represent the first example of cells uniquely or prevalently expressing only the D-2L receptor, conceivably coupled to its native transduction mechanisms. These considerations prompted us to evaluate the pharmacology and the second messenger systems known to be modulated by dopamine. Scatchard analysis of [H-3]spiperone binding resulted in a linear plot, consistent with the existence of a single class of binding sites, with a K-d of 0.055 +/- 0.002 nM and a B-max of 27 +/- 3.5 fmol/mg protein. Competition experiments confirmed the GTP-dependence and the order of potency for agonist and antagonist ligands consistentwith binding to a D-2 receptor. The inhibitory effects of dopamine onadenylyl cyclase activity, inositol phosphate production and intracellular free calcium concentrations, the latter presumably via the opening of K+ channels, and prolactin secretion, as well as the reversal ofthe effect by the D-2-selective antagonist (-)sulpiride and pretreatment with pertussis toxin, are consistent with the known biological actions of dopamine at D-2 receptors. Based on our observations, the MMQ cell line can be considered a useful tool for investigating ligand-receptor interactions to develop new selective dopaminergic D-2L ligands for the therapy of dopamine-related disorders such as schizophrenia, depression, Parkinson's disease and drug addiction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 01:10:32