[Effects of dynorphin A and CCK-8 on synaptosomal 45Ca uptake of the rat spinal cord]

Cholecystokinin octapeptide (CCK-8) and angiotensin I (AI) have been shown in behavioral studies being endogenous antiopioid substrates (AOS). To assess their antiopioid mechanism at postreceptor level, we observed the effects of the three opioids and the two AOS on 45Ca uptake of the rat spinal synaptosomal preparations. Morphine, Dyn A and DPDPE at concentrations of 10 nmol/L to 1 mumol/L, produced a mild suppression of 45Ca uptake of synaptosomal preparations from ventral spinal cord. CCK-8 showed a mild suppression only at a concentration of 1 mumol/L. In synaptosomes prepared from dorsal spinal cord, Dyn A but not morphine or DPDPE, produced a strong inhibition of 45Ca uptake which was blocked by nor-BNI, a kappa receptor antagonist, at 1 mumol/L. While CCK-8 (10 nmol/L to 1 mumol/L) also suppressed 45Ca uptake, it could antagonize the suppressive effect induced by Dyn A. In contrast to CCK-8, AI (10 nmol/L to 1 mumol/L) influenced neither on synaptosomal 45Ca uptake, nor on Dyn A suppression of 45Ca uptake. The results presented above fit very well with our behavioral studies, i.e., CCK-8 antagonized opioid analgesia in both the brain and the spinal cord, whereas AI antagonized opioid analgesia in the brain but not in the spinal cord. It is therefore concluded that antagonism of the opioid suppression of synaptosomal 45Ca uptake might be one of the mechanisms for the antiopioid activity of CCK-8 and AI.