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Human D2 and D4 Dopamine Receptors Couple Through Betagamma G-protein Subunits to Inwardly Rectifying K+ Channels (GIRK1) in a Xenopus Oocyte Expression System: Selective Antagonism by L-741,626 and L-745,870 Respectively

Human D2 and D4 Dopamine Receptors Couple Through Betagamma G-protein Subunits to Inwardly Rectifying K+ Channels (GIRK1) in a Xenopus Oocyte Expression System: Selective Antagonism by L-741,626 and L-745,870 Respectively

G Pillai, N A Brown, G McAllister, G Milligan, G R Seabrook

Neuropharmacology. 1998 Aug;37(8):983-7.

PMID: 9833627

Abstract:

To examine the effects of a novel selective D4 receptor ligand, L-745,870 (3-[4-(4-chlorophenyl)piperazin-1-yl]methyl-1H-pyrrolo[2,3-b]pyrid ine), on human dopamine receptor function, the ability of this ligand to antagonise G-protein gated inwardly rectifying K+ (GIRK/Kir3) currents activated by cloned human D2 and D4 receptors expressed in Xenopus oocytes was examined using voltage-clamp recording. Its effects were also contrasted with that of a selective D2 receptor antagonist L-741,626. L-745,870 had no detectable agonist activity on human D4 receptors and selectively blocked currents activated by D4 but not D2 receptors. The role of G-protein subunits in dopamine receptor modulation of GIRK currents was also examined by co-expression of beta1 and/or gamma2 subunits on spontaneously active and receptor-activated currents. Currents activated by both D2 and D4 receptors were occluded by direct activation of GIRK currents following co-transfection with the cDNA encoding G-protein betagamma subunits. These data demonstrate that L-745,870 and L-741,626 act as antagonists on human D4 and D2 receptors respectively, and that activation of GIRK channels by these dopamine receptors can be disrupted by direct stimulation of K+ currents by G-protein betagamma subunits.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP81226600	L-741,626		81226-60-0	Price

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