Effects of amino acids, especially taurine and γ-aminobutyric acid (GABA), on analgesia and calcium depletion induced by morphine in mice

Abstract

The analgesic effect of morphine was antagonized in mice by intracerebroventricular pretreatment with taurine, γ-aminobutyric acid (GABA) or glycine and was potentiated by ethylene glycol tetra-acetic acid (EGTA) but not altered by L-glutamate or L-aspartate. The potentiation of morphine analgesia by EGTA was reversed by a concentration of taurine that did not alter the tail-flick response. The selective depletion of 45Ca 2+ from synaptic vesicles observed with morphine administration was significantly inhibited by taurine injection (1.2 μmol/brain, i.vt.) but was not altered by the same dose of GABA. Inhibition of ATP-dependent 45Ca 2+ uptake in synaptosomes by morphine was also completely reversed by taurine (10 −2 M) which by itself did not alter 45Ca 2+ uptake. These results suggest that antagonism of morphine analgesia by taurine may be caused by blockade of the morphine-induced inhibition of both ATP-dependent synaptosomal 45Ca 2+ uptake and changes in synaptic vesicular 45Ca 2+ localization, while the antagonism by GABA was not associated with synaptosomal Ca 2+.