Lithium attenuates the effects of dynorphin A(1-13) on inositol 1,4,5-trisphosphate and intracellular Ca2+ in rat ventricular myocytes.

Abstract

When rat ventricular myocytes were stimulated with dynorphin A(1-13), a transient and rapid increase followed by a sustained and prolonged elevation in the intracellular levels of inositol 1,4,5-trisphosphate ¿Ins(1,4,5)P3¿ was observed. The responses were dose-related and abolished by nor-binaltorphimine. In the presence of lithium and absence of extracellular free inositol, the initial rapid elevation in Ins(1,4,5)P3 remained the same, but the second phase of sustained and prolonged elevation was abolished. Under this condition, the elevation in cytosolic free Ca2+ ([Ca2+]i) was reduced significantly although there was still a detectable elevation over a time period when the Ins(1,4,5)P3 was at the basal level. The responses in Ins(1,4,5)P3 and [Ca2+]i were not affected by lithium when stimulation of ventricular myocytes with dynorphin A(1-13) was performed in the presence of extracellular inositol. The data suggest that in rat ventricular myocytes, the kappa-opioid receptor agonist stimulated mobilization of [Ca2+]i was mediated mainly by Ins(1,4,5)P3.