Evidence for a Direct Negative Coupling between Dopamine-D2 Receptors and PLC by Heterotrimeric Gi1/2 Proteins in Rat Anterior Pituitary Cell Membranes
2002; Oxford University Press; Volume: 143; Issue: 3 Linguagem: Inglês
10.1210/endo.143.3.8697
ISSN1945-7170
AutoresRamahefarizo Rasolonjanahary, Corinne Gérard, Marie-Noëlle Dufour, Vincent Homburger, A Enjalbert, Gilles Guillon,
Tópico(s)Protein Kinase Regulation and GTPase Signaling
ResumoDopamine (DA) is known to inhibit basal and hormone TRH- or angiotensin II (AngII)-stimulated PRL secretion and inositol phosphate accumulation in rat pituitary cells in primary culture. This inhibition persists when cells are incubated in a calcium-free medium (a condition in which DA could not inhibit PLC activities by blocking calcium influx) and is abolished by a Pertussis toxin treatment. These data suggest that DA receptor could be negatively coupled to PLC by a direct mechanism involving a Pertussis toxin-sensitive G protein. To demonstrate this hypothesis, we measured PLC activities on crude plasma membranes obtained from rat pituitary cells in primary culture grown in the presence of tritiated myo-inositol. We showed that 1) DA and quinpirole or RU24926 (specific D2 agonists) inhibited both basal and TRH- or AngII-stimulated membrane PLC activities. 2) Such inhibitions were completely prevented by sulpiride (specific D2 antagonist). 3) Heterotrimeric Gi1/2 proteins coupled the DA receptors to PLC because DA inhibitions were completely reversed by preincubation either with Pertussis toxin or with a specific G(alpha)i1/(alpha)i2 antibody. Such data are in favor of the existence of a direct negative coupling between DA-D2 receptor and PLC on a native physiological plasma membrane model.
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