Relationship between the actions of calcium ions, opiods, and prostaglandin E1 on the level of cyclic AMP in neuroblastoma x glioma hybrid cells.

Abstract

Abstract: Neuroblastoma × glioma hybrid cells increase their intracellular concentration of cyclic AMP in response to prostaglandin E1 (PGE1). This effect is inhibited by opioids. The response to PGE1 is positively correlated with the concentration of Ca2+ in the incubation medium. The Ca2+ antagonists Co2+ and La3+, the Ca2+ chelator EGTA and a blocker of Ca2+ influx into cells, Segontin, inhibit the response to PGE1. At low external concentrations of Ca2+ the response to PGE1 is enhanced by the Ca2+ ionophore A23187. The effects of A23187 and Segontin point to a cytosolic site of Ca2+ action. Lack of Ca2+ reduces the level of cyclic AMP even in the absence of PGE1 and the presence of an inhibitor of cyclic AMP phosphodiesterase. Ca2+ is required even for an increase in the level of cyclic AMP in cells pretreated with cholera toxin. The increases in level of cyclic AMP evoked by PGE, in a neuroblastoma and by PGE1 or noradrenaline in a glioma cell line do not depend on Ca2+. The response of the hybrid cells to the opioid leucine‐enkephalin appears not to rely on the presence of Ca2+. Even changing the intracellular concentration of Ca2+ by the ionophore A23187 does not alter the effect of the opioid. The analogy between opioids and lack of Ca2+ in the short‐term (minutes) experiments mentioned holds also for long‐term (hours) experiments. Cells chronically exposed to opioids or to low concentrations of Ca2+ display an enhanced maximal response to PGE1.