Ca²⁺ transmembrane fluxes and nerve growth factor action on a clonal cell line of rat phaeochromocytoma

Abstract

Nerve growth factor (NGF) is a polypeptide hormone which has a fundamental role in the development and maintenance of sympathetic and some sensory neurones^1,2. The primary event by which NGF exerts its actions on these neurones probably involves the recognition of specific membrane-located receptors^3–5. A clonal cell line of rat phaeochromocytoma, PC12, responds to NGF by cessation of division and expression of several properties characteristic to mature sympathetic neurones, including neurite outgrowth^6,7. These cells also possess cell-surface NGF receptors, a fraction of which are occupied at NGF concentrations which elicit NGF-specific responses in these cells (G.L. and E.M.S., unpublished results). The manner in which binding of NGF to its receptor is translated into the subsequent morphological and biochemical events is not yet known but is being investigated. One possible transducing mechanism which has been suggested involves transient changes of intracellular cyclic AMP levels^8,9. The divalent cation Ca²⁺ has been proposed as a second messenger in the mechanism of action of peptide hormones such as insulin^10,11, which also initiates its action through membrane-bound receptors. Here, we have investigated the hypothesis that the mechanism of NGF action on PC12 cells may involve modulation of calcium transmembrane fluxes. The evidence shows that NGF has no significant influence on calcium fluxes as measured by uptake and efflux rates of ⁴⁵Ca in PC12 cells.