Selectivity of various opioid peptides towards delta-, kappa; and mu-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain.
The selectivity of a series of opioid peptides towards the mu-, delta- and kappa-opioid receptors mediating differential inhibition of electrically-induced neurotransmitter release from rat brain slices was studied, viz. cortical [3H]noradrenaline release (inhibited via mu-receptors), striatal [3H]dopamine release (inhibited via kappa-receptors) and striatal [14C] acetylcholine release (inhibited via delta-receptors). The highest affinity pD2 7.4) and selectivity towards mu-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 delta-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 delta-opioid receptors. Both dynorphin(1-13) and dynorphin(1-8) exhibited a high affinity for kappa-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 mu-receptors (pD2 6.7-6.8), but dynorphin(1-8), in contrast to dynorphin(1-13), also displayed a high affinity to delta-receptors (pD2 7.6).
Mulder
A H
AH
Department of Pharmacology, Free University Medical Faculty, Amsterdam, The Netherlands.
Wardeh
G
G
Hogenboom
F
F
Frankhuyzen
A L
AL
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*
D004745:Enkephalins; D018377:Neurotransmitter Agents; D011957:Receptors, Opioid; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D004399:Dynorphins; D000324:Adrenocorticotropic Hormone; D004298:Dopamine; D009638:Norepinephrine