Modulation of 5-HT1A receptor activation by its interaction with wild-type and mutant Gαi3 proteins
作者： Delphine S Dupuis , Thierry Wurch , Stéphanie Tardif , Francis C Colpaert , Petrus J Pauwels
DOI: 10.1016/S0028-3908(00)00098-8
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摘要: Constitutive and agonist-dependent activation of the recombinant human 5-HT(1A) receptor (RC: 2.1.5HT.01A) was investigated by co-expression with a rat G(alphai3) protein in Cos-7 cells. The interaction between modulated substitution site for pertussis toxin-catalysed ADP-ribosylation (cysteine(351)) each natural amino acids. Enhanced basal [(35)S]GTPgammaS binding responses (+24 to +189%) were observed mutant proteins containing at position 351 either histidine, glutamine, serine, tyrosine or nonpolar acid exception proline. With these proteins, spiperone (10 microM), but not WAY 100635 reduced (-22 -60%, p<0.05) enhanced response. 5-HT microM)-mediated attained some G(alphai3)Cys(351) (Phe, Met, Val Ala) more than 300% that obtained wt protein. Similar results also prototypical agonist 8-OH-DPAT partial (-)-pindolol. Fusion assembled from G(alphai3)Cys(351), G(alphai3)Cys(351)Gly G(alphai3)Cys(351)Ile displayed similar observations ligands as proteins. Both degree (-)-pindolol, its inhibition spiperone, strongly correlate (r(2): 0.78-0.81) octanol/water partition coefficients mutated present data suggest does result maximal agonists being investigated.
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