Kappa-receptor mechanisms in synaptosomal Ca uptake

1. Inhibition of Ca uptake by certain opioids was tested in synaptosomes of rat brain. The potency order was dynorphin A 1-13, a kappa-selective agonist greater than nalorphine greater than nalorphine epoxide greater than morphine. 2. The pA2 values (negative logarithms of dissociation constant) of naloxone against four opioids were not significantly different from each other, suggesting that the site of action of the four opioids is identical. 3. Morphiceptin, a mu-selective agonist and DADLE, a delta-selective agonist had no effect on Ca uptake. 4. These results suggest that the site of action of the four opioids is kappa-receptors. 5. Potency order estimated from competition inhibition curves of specific binding of [3H]ethylketo-cyclazocine (kappa-selective ligand) by the test opioids was nalorphine greater than nalorphine epoxide greater than dynorphin A 1-13 greater than morphine. 6. The difference between the two potency orders suggests that affinities and intrinsic activities of the drugs are important factors in determining their agonistic activity in kappa-receptor mechanisms.