MODIFICATION OF ENDORPHIN/ENKEPHALIN ANALGESIA AND STRESS‐INDUCED ANALGESIA BY DIVALENT CATIONS, A CATION CHELATOR AND AN IONOPHORE

Abstract

1 The possibility that divalent cations may antagonize opiate peptide analgesia and stress-induced analgesia was examined. 2 Intracerebroventricular injection of low doses of Ca²⁺, Mn²⁺ and Mg²⁺ antagonized β-endorphin and methionine-enkephalin analgesia. Ba²⁺ and Cd²⁺ were without effect. 3 The ionophore, A23187, significantly antagonized β-endorphin analgesia and the effect was increased when a low dose of Ca²⁺ was injected at the same time as the ionophore. 4 Ethylene glycol tetraacetic acid (but not ethylenediamine tetraacetic acid) significantly potentiated endorphin analgesia. 5 Stress-induced analgesia, as determined by increased tail-flick latencies following intraperitoneal injection of acetic acid, was effectively antagonized by naloxone, Ca²⁺ and Mn²⁺. The frequency of writhing following acetic acid injection was increased by both naloxone and divalent metal ions, again suggesting antagonism of endogenous opiates. 6 These results confirm previous findings indicating that divalent metal ions (and especially Ca²⁺) may be involved in the actions of opiates.