Absence of coupling between D2 dopamine receptors and calcium channels in lactotrophs from cycling female rats

James Rendt, Gerry S. Oxford

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Abstract

Recent evidence suggests that an important mechanism underlying the inhibition of PRL secretion by dopamine in the anterior pituitary is a direct inhibition of current through voltage-gated calcium channels. An alternative mechanism involves the activation of G protein-coupled potassium channels by D2 receptor activation, infsequent hyperpolarization of the lactotroph membrane, and an indirect inhibition of calcium influx as spontaneous electrical activity is reduced. Using patch voltage clamp methods, we have reexamined the effect of D2 receptor activation on calcium currents (ICa) in pituitary cells from normal cycling female rats and in GH4Cl pituitary tumor cells expressing cloned D2 receptors. Furthermore, we have examined secretory responses using a single cell immunoblot method. Dopamine (0.1-10 μM) failed to significantly inhibit ICa in either GH4Cl cells or normal female lactotrophs. Similarly, the D2 agonist quinpirole (20-100 μM) did not reduce ICa in lactotrophs. No responses to D2 agonists were seen when barium was infstituted for calcium or when experiments were performed using the nystatin-permeabilized patch technique to avoid loss of intracellular macromolecules. Quinpirole also failed to inhibit ICa in lactotrophs isolated from lactating female rats. We have thus far been unable to observe a significant inhibition of ICa by activation of D2 receptors. PRL secretion assessed by immunoblotting methods was dramatically inhibited by quinpirole at normal (5 mM) extracellular K+. However, in elevated (50 mM) K+ that depolarizes the cells and activates calcium channels, quinpirole produced only a very modest inhibition of secretion. We conclude that direct inhibition of ICa by D2 receptor activation is not a major mechanism underlying the dopaminergic inhibition of PRL, secretion in normal female lactotrophs.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalEndocrinology
Volume135
Issue number2
DOIs
StatePublished - Aug 1994

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ASJC Scopus subject areas

  • Endocrinology

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