Mobilization of calcium from intracellular store as a possible mechanism underlying the anti-opioid effect of angiotensin II

Abstract

Angiotensin II (AII), injected intracerebroventricularly, has been shown to antagonize opioid analgesia. The mechanism for this was obscure. In the neuroblastoma X glioma NG 108-15 hybrid cell line, the K +-induced increase in [Ca 2+]i can be suppressed by the delta opioid agonist [D-Pen 2, D-Pen 5]enkephalin (DPDPE) at 0.01–1 μM, an effect completely reversed by the opioid antagonist naloxone. Angiotensin II (AII) at concentrations of 0.1 and 1 μM mobilized free Ca 2+ from an intracellular pool, and this effect was antagonized by the AII receptor antagonist saralasin. AII (1 μM) had no significant effect on the increase in [Ca 2+]i induced by K +, but it blocked the suppressive effect of DPDPE on the K +-induced [Ca 2+]i increase. The results indicate that mobilization of intracellular calcium may underlie the anti-opioid effect of AII.