Inhibitory actions of opioid compounds on calcium fluxes and neurotransmitter release from mammalian cerebral cortical slices

Abstract

1 The effects of opioid agonists on veratrine-stimulated Ca²⁺ influx and amino acid neurotransmitter release in rat cerebrocortical brain slices were studied. Inhibitory effects were seen on both of these parameters with all of the opioid agonists used. 2 None of the drugs used affected basal ⁴⁵Ca²⁺ uptake, basal K⁺ content or basal amino acid release from the slices. 3 At high concentrations (100 μM) fentanyl, tifluadom, U50,488H, butorphanol and bremazocine greatly inhibited the depolarization of the slices by veratrine as determined by the reduced release of K⁺. 4 The opioid receptor subtypes at which the drugs were acting were characterized by the antagonistic effects of naloxone and WIN44441-3. 5 The opioid-induced inhibition of stimulated Ca²⁺ uptake and amino acid release were not antagonized by WIN44441-2, the inactive enantiomer of WIN44441-3. 6 It is concluded that opioid agonists acting through μ- and k-receptors and probably through δ- and s̀-receptors, have an inhibitory effect on Ca²⁺ uptake into cerebrocortical brain slices and the subsequent release of aspartate, glutamate and γ-aminobutyric acid (GABA).