Characterization of [H-3]nisoxetine binding in rat vas deferens membranes: Modulation by sigma and PCP ligands.

Pubill, D; Gasulla, D; Sureda, FX; Camins, A; Pallas, M; Escubedo, E; Camarasa, J


Sigma (sigma) and phencyclidine (PCP) receptor ligands, apart from their main effects on sigma receptors and NMDA receptor-mediated neurotransmission, have been found to interact with catecholamine systems in several central and peripheral tissues. In the present study the binding profile of [H-3]nisoxetine ([H-3]NIS), a selective marker of the noradrenaline transporter, has been characterized in rat vas deferens membranes to further study its modulation by a number of characteristic sigma and PCP ligands. The binding of [H-3]NIS was found to be of high affinity (K-d = 1.63 +/- 0.36 nM), saturable, sodium-dependent and to a single population of binding sites (n(H) = 1.003 +/- 0.017). The maximal binding capacity was 1,625 +/- 500 fmol/mg of protein. Kinetic experiments gave a k(+1) of 3.9.10(7) min(-1)M(-1) and a k(-1) of 0.005 min(-1). The [H-3]NIS binding was totally inhibited, with IC50 values in the micromolar range, by all the sigma and PCP ligands tested, with the following order of potency: haloperidol > dextromethorphan > dizocilpine > dextrorphan > (+)-3-PPP > PCP > tenocyclidine. This order correlates well with that described in other tissues using [H-3]desmethylimipramine. The inhibition by all these compounds, except that of (+)-3-PPP, was competitive. These results suggest that sigma and PCP ligands bind, at low micromolar concentrations, to a site in the noradrenaline transporter that is labelled by [H-3]NIS.

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Título según WOS: ID WOS:000071670300007 Not found in local WOS DB
Título de la Revista: LIFE SCIENCES
Volumen: 62
Número: 8
Fecha de publicación: 1998
Página de inicio: 763
Página final: 773


Notas: ISI