Signal Transduction in Rana Melanotrope Cells: Mechanism of Action of Neurotensin on Secretory and Electrical Activities
Abstract
The pars intermedia of the frog (Rana esculenta) pituitary, which is composed of a single population of endocrine cells, the melanotrophs, is a very suitable model to study the mode of action of hypophysiotropic neuropeptides. We have recently characterized neurotensin (NT) in Rana esculenta and found that synthetic frog NT (fNT) stimulates the electrical and secretory activities of melanotrophs. By combining biochemical, pharmacological, microfluorimetric, and electrophysiological approaches, we observed that NT stimulates inositol-trisphosphate production that provokes Ca(2+) release from intracellular stores. The resulting increase in cytosolic Ca(2+) concentration ([Ca(2+)](c)) activates the secretion of alpha-melanocyte-stimulating hormone (alpha-MSH), stimulates Ca(2+)-dependent protein kinase (PKC) activity, and provokes a depolarizing chloride efflux. PKC reduces the amplitude, whereas membrane depolarization increases the frequency of L- and N-type Ca(2+) currents underlain by the action potential discharge. The complex regulatory processes exerted by NT on Ca(2+) signaling likely generate discrete variations in the [Ca(2+)](c) at various distances from secretory vesicles, contributing to the fine-tuning of alpha-MSH secretion.