Neuroendocrinology 2004 Jan 01;806:368-78. doi: 10.1159/000084144.

Dopamine D2-receptor activation differentially inhibits N- and R-type Ca2+ channels in Xenopus melanotrope cells.

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Dopamine inhibits pituitary melanotrope cells of the amphibian Xenopus laevis through activation of a dopamine (D2) receptor that couples to a Gi protein. Activated Gi protein subunits are known to affect voltage-operated Ca2+ currents (ICa). In the present study we investigated which Ca2+ currents are regulated by D2-receptor activation and which Gi protein subunits are involved. Whole-cell voltage-clamp patch-clamp experiments from holding potentials (HPs) of -80 and -30 mV show that 28.6 and 36.9%, respectively, of the total ICa was inhibited by apomorphin, a D2-receptor agonist. The inhibited current had fast activation and inactivation kinetics. From an HP of -80 mV, inhibition of N-type Ca2+ currents with omega-conotoxin GVIA and R-type current by SNX-482 reduced the efficacy of the apomorphin-induced inhibition. From an HP of -30 mV this reduction for omega-conotoxin GVIA was still observed. Blocking L-type current by nifedipine or P/Q-type current by omega-agatoxin IVA did not affect apomorphin-induced inhibition at either HP. Our results imply that D2-receptor activation inhibits both N- and R-type Ca2+ currents. Using a strong depolarizing pre-pulse partially reversed the inhibition of the total current by apomorphin. About 50% of this inhibition was achieved through interaction of Gbeta/gamma proteins, and this part of the inhibited ICa had fast activating and inactivating kinetics. However, the other part of the current inhibited by D2-receptor activation may proceed through Galpha-PKA phosphorylation.

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Species referenced: Xenopus laevis
Genes referenced: anxa7 ap3b1 suclg1 suclg2