Neurotensin-induced Cl − current in guinea-pig dorsal root ganglion cells

Abstract

In guinea-pig dorsal root ganglion cells held under voltage-clamp at −80 mV, neurotensin elicited an inward current ( I NT) whose amplitude increased with increasing neurotensin concentration (40–4000 nM). The effect was blocked by a nonpeptide neurotensin antagonist. I NT occurred in the absence of the extracellular Na +, but not in the absence of the intracellular Cl −, and it was outward directed by reversing the driving force for Cl −. I NT, like the γ-amino-butyric acid (GABA)-induced Cl − current ( I GABA), remained little changed after virtual elimination of cytosolic free-ionized Ca 2+ or after treatment with a Ca 2+-activated Cl − channel blocker, but, in contrast to I GABA it was resistant to the I GABA blocker picrotoxin, slower in time course and more easily desensitized when repeatedly elicited. I NT and I GABA were additive to each other. AG-protein inhibitor markedly reduced I NT, and a G-protein activator produced an inward current during which no current could be elicited by neurotensin. These results show that neurotensin exerts an effect to activate Ca 2+-insensitive Cl − channels distinct from those activated by GABA in guinea-pig dorsal root ganglion cells, and the effect may arise through a G-protein-dependent mechanism.