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Neuropharmacology. 2002 May;42(6):855-63.

Evidence for protean agonism of RX 831003 at alpha 2A-adrenoceptors by co-expression with different G alpha protein subunits.

Author information

1
Centre de Recherche Pierre Fabre, Department of Cellular and Molecular Biology, 17, avenue Jean Moulin, 81106 Castres Cedex, France. peter.pauwels@pierre-fabre.com

Abstract

Intrinsic properties of alpha(2) AR ligands were investigated by measuring two distinct signalling pathways via the alpha(2A) AR protein in CHO-K1 cells: (i) a Ca(2+) response mediated by a promiscuous G(alpha 15) protein; and (ii) a pertussis toxin-resistant [(35)S]GTP gamma S binding response mediated by a G(alpha o)Cys(351)Ile protein. The dexefaroxan analogue RX 831003 was virtually without intrinsic activity at the wt alpha(2A) AR via a G(alpha 15) protein, but induced a partial positive Ca(2+) response [pEC(50): 7.79 (0.17), E(max): 38+/-1% vs (-)-adrenaline] at the mutant Thr(373L)ys alpha(2A) AR. RX 831003 displayed a similar potency (pIC(50): 7.68 (0.21) for both the wt (E(max): -18+/-4%) and Thr(373)Lys alpha(2A) AR (E(max): -19+/-4%) inhibition of basal [(35)S]GTP gamma S binding via a G(alpha o)Cys(351)Ile protein. These data indicate that the alpha(2) AR ligand RX 831003 behaves as a protean agonist at the alpha(2A) AR and that its activity is highly dependent on the co-expressed G(alpha) protein subunit.

PMID:
12015212
[Indexed for MEDLINE]

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