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Am J Physiol Endocrinol Metab 277: E73-E80, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 1, E73-E80, July 1999

The sigma -ligand (+)-pentazocine depresses M current and enhances calcium conductances in frog melanotrophs

O. Soriani1,2, F. le Foll1, L. Galas1, F. Roman2, H. Vaudry1, and L. Cazin1

1 European Institute for Peptide Research, Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale U413, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides no. 23, Unité Associée Centre National de la Recherche Scientifique, University of Rouen, 76821 Mont-Saint-Aignan; and 2 Institut de Recherche Jouveinal/Parke-Davis, 94265 Fresnes, France

Gramicidin-perforated patch clamp experiments and microfluorimetric measurements were performed to study the ionic mechanisms involved in the sigma -receptor-mediated stimulation of frog (Rana ridibunda) pituitary melanotrophs. The sigma -ligand (+)-pentazocine (50 µM) depressed a sustained outward K+ current. The kinetic properties of this K+ component, investigated by analyzing tail currents, were reminiscent of those of the M current (IM), with an activation threshold close to -60 mV, a -21-mV half-maximal activation potential, and two-component exponential deactivation kinetics at -90 mV. (+)-Pentazocine (20 µM) produced a 12-mV rightward shift of the activation curve and accelerated the deactivation rate of the tail current. It is also demonstrated that (+)-pentazocine (20 µM) reversibly increased both voltage-dependent calcium conductances and internal calcium level. Altogether, these results suggest that the sigma -receptor-induced modulation of IM and calcium currents likely underlies the increase of intracellular [Ca2+].

sigma -receptors; calcium channels; patch-clamp technique; melanotrophs; (+)-pentazocine


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