Dopaminergic system mediates only delta-opiate inhibition of endogenous acetylcholine release evoked by glutamate from rat striatal slices.
In order to study the role of the dopaminergic system in the mu- or delta-opioid inhibition of endogenous acetylcholine release evoked by glutamate, we blocked the dopaminergic transmission with dopaminergic antagonists and/or 6-hydroxydopamine lesions. In all these experimental conditions we show that dopaminergic antagonists by themselves could not modify the glutamate-evoked acetylcholine release, and the selective D1 antagonist (SCH 23390) was unable to modify the mu- or delta-opioid inhibition of glutamate-evoked acetylcholine release. However, in the non-lesioned animals and in the contralateral striata to 6-hydroxydopamine lesions, D2 antagonists (haloperidol or sulpiride, 10 microM) prevented the effects of delta-opiate agonists ([D-Ala2, D-Leu5]enkephalin, 1 microM and [D-Pen2, D-Pen5]enkephalin, 0.1 microM), but not the effects of mu-opiate agonists (morphine or [D-Ala2, Gly(ol)5]enkephalin, 1 microM). Furthermore, [D-Ala2, D-Leu5]enkephalin inhibition of glutamate-evoked acetylcholine release was prevented by D2 antagonists in a concentration-dependent manner. Instead, in the 6-hydroxydopamine-lesioned side, while [D-Ala2, D-Leu5]enkephalin (1 microM) inhibition of glutamate-evoked acetylcholine release was completely abolished, morphine (1 microM) inhibition remained unchanged. We conclude that the inhibition of glutamate-evoked endogenous acetylcholine release by delta-opiate agonists, unlike mu-opiate agonists, depends on dopaminergic terminals and D2 receptors. Furthermore, these results suggest that the inhibition by delta-opiate agonists could be the result of dopamine release from dopaminergic terminals and its action on D2 receptors.
Departament de Biologia Cellular i Anatomia Patològica, Hospital de Bellvitge, Facultat de Medicina, Universitat de Barcelona, Spain.
E
E
Arenas
J
J
Alberch
J
J
Marsal
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D008297:Male; D009020:Morphine / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D012636:Secretory Rate / Q000187:drug effects
D001552:Benzazepines; D004745:Enkephalins; D005971:Glutamates; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D016627:Oxidopamine; D000109:Acetylcholine; D004298:Dopamine