Selectivity of various opioid peptides towards delta-, kappa; and MU-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain

Abstract

The selectivity of a series of opioid peptides towards the μ-, δ- and κ-opioid receptors mediating differential inhibition of electrically-induced neurotransmitter release from rat brain slices was studied, viz. cortical [3H]noradrenaline release (inhibited via μ-receptors), striatal [3H]dopamine release (inhibited via κ-receptors) and striatal [14C] acetylcholine release (inhibited via δ-receptors). The highest affinity pD2 7.4) and selectivity towards μ-receptors was exhibited by Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO), whereas [D-Pen2, D-Pen5]enkephalin (DPDPE) was found to be the most selective δ-receptor agonist (pD2 7.3). Also the hexapeptides [D-Ser2]Leu-enkephalin-Thr (DSLET) and [D-Thr2]Leu-enkephalin-Thr (DTLET) showed a relatively high selectivity and, in addition, a high affinity (pD2 8.2-8.4) for δ-opioid receptors. Both dynorphin(1-13) and dynorphin(1-8) exhibited a high affinity for κ-receptors (pD2 resp. 8.3 and 8.0), but the latter was far less selective. Both of the dynorphin A-related peptides showed affinity to μ-receptors (pD2 6.7-6.8), but dynorphin(1-8), in contrast to dynorphin(1-13), also displayed a high affinity to δ-receptors (pD2 7.6). © 1989.