Relationship between synaptosomal calcium uptake and antinociceptive action of morphine

We studied the relationship between inhibition of 45Ca2+ uptake and the antinociceptive action induced by morphine and effects of papaverine and 1,1-diphenyl-3-piperidinobutanol hydrochloride (Aspaminol) on both these actions of morphine. Addition of these drugs in the incubation medium significantly inhibited glutamate-stimulated synaptosomal 45Ca2+ uptake. The inhibition curves of morphine and Aspaminol on glutamate-stimulated synaptosomal 45Ca2+ uptake were linear, but that of papaverine was not. The inhibition of morphine on synaptosomal 45Ca2+ uptake was reversed by addition of naloxone. The inhibition of synaptosomal 45Ca2+ uptake induced by morphine was increased by the simultaneous addition of Aspaminol, but the inhibition induced by both morphine and papaverine was not increased to more than that by papaverine alone. Since morphine-antinociception was potentiated by Aspaminol and blocked by papaverine, these results support that the inhibition of synaptosomal calcium uptake plays an important role in the production of morphine-antinociception. However, since the inhibition of synaptosomal 45Ca2+ uptake by morphine was less than that by both Aspaminol and papaverine, and papaverine blocked morphine-antinociception, notwithstanding that 10(-4) M of papaverine alone completely inhibited glutamate-stimulated 45Ca2+ uptake into synaptosomes, it may be difficult to account for the antinociceptive action of morphine by the inhibition of 45Ca2+ uptake only.