A-Current down-modulated by sigma receptor in frog pituitary melanotrope cells through a G protein-dependent pathway

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 289; no. 1; pp. 321 - 328
• Main Authors: Soriani, O, Foll, F L, Roman, F, Monnet, F P, Vaudry, H, Cazin, L
• Format: Journal Article
• Language: English
• Published: United States 01.04.1999
• Subjects: Animals; Anisoles - pharmacology; Cells, Cultured; Cinnamates - pharmacology; Cyclopropanes - pharmacology; Down-Regulation; Electrophysiology; GTP-Binding Proteins - physiology; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Ligands; Melanocyte-Stimulating Hormones - physiology; Membrane Potentials - drug effects; Patch-Clamp Techniques; Pentazocine - pharmacology; Pituitary Gland - cytology; Pituitary Gland - physiology; Potassium Channels - physiology; Propylamines - pharmacology; Rana ridibunda; Receptors, sigma - agonists; Receptors, sigma - antagonists & inhibitors; Receptors, sigma - physiology; Signal Transduction - physiology
• ISSN: 0022-3565

Gramicidin perforated patch-clamp recordings were used to study the effects of two sigma 1 receptor ligands, (+)-N-cyclopropylmethyl-N-methyl-1, 4-diphenyl-1-ethyl-but-3-en-1-ylamine hydrochloride (JO 1784) and (+)-pentazocine, on the transient outward potassium current (IA) in cultured frog melanotrope cells. (+)-Pentazocine reversibly decreased the current amplitude in a dose-dependent manner. The effects of (+)-pentazocine were mimicked by JO 1784 and were markedly reduced by the sigma 1 receptor antagonist, N, N-dipropyl-2-[4-methoxy-3-2(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE 100). Inactivation rate of IA was best fitted with a double exponential function, yielding time constants of 23.7 and 112.5 ms. (+)-Pentazocine (20 microM) accelerated the current decay, decreasing the time constants to 10.7 and 59 ms, respectively. Current-voltage experiments revealed that (+)-pentazocine (20 microM) did neither modify the open-state I/V curves nor the voltage dependence of IA. However, (+)-pentazocine (20 microM) shifted the steady-state inactivation curve toward more negative potentials and increased the time constant of the time-dependent removal of inactivation. In whole-cell experiments, internal dialysis of guanosine-5'-O-(3-thiophosphate) (100 microM) irreversibly prolonged the response to (+)-pentazocine. In addition, cholera toxin pretreatment (1 microgram. ml-1; 12 h) suppressed the inhibition of IA by (+)-pentazocine (20 microM). It is concluded that in frog melanotrope cells, a cholera toxin-sensitive, G protein-dependent inhibition of IA through a sigma 1 receptor activation, at least partially, underlies the excitatory effect of sigma ligands.