No evidence for presynaptic opioid receptors on cholinergic, but presence of kappa-receptors on dopaminergic neurons in the rabbit caudate nucleus: involvement of endogenous opioids.
The effects of various opioid receptor agonists and antagonists were studied in rabbit caudate nucleus slices preincubated with either [3H]dopamine or [3H]choline, superfused with medium (containing in most experiments the D2 receptor antagonist domperidone) and subjected to electrical field stimulation. The stimulation-evoked [3H]overflow from slices prelabeled with [3H]dopamine (evoked [3H]dopamine release) was significantly reduced by preferential kappa-opioid receptor agonists, like U-50,488 H, but not by mu- or delta-opioid receptor selective drugs. Opioid receptor antagonists shifted the concentration/response curve of U-50,488 H to the right (apparent pA2-value of the kappa-selective antagonist nor-binaltorphimine: 10.1) and enhanced the evoked dopamine release in the presence of a mixture of peptidase inhibitors. On the other hand, the [3H]overflow from rabbit caudate nucleus slices prelabeled with [3H]choline (evoked acetylcholine release) remained almost unaffected by any opioid receptor agonist, as long as the presynaptic D2 heteroreceptor was blocked with domperidone: in the absence of domperidone, U-50,488 H exhibited facilitatory effects. For comparison, the effects of the preferential delta-opioid receptor agonist DPDPE was also studied in slices of the rat striatum, where it clearly inhibited the evoked acetylcholine release. From our data we conclude that in the rabbit caudate nucleus the evoked dopamine release is inhibited by both exogenous and endogenous opioids via presynaptic kappa-opioid receptors, whereas the evoked release of acetylcholine is not, or only indirectly (via released dopamine) affected by opioids.
Jackisch
R
R
Pharmakologisches Institut, Universität Freiburg, Germany.
Hotz
H
H
Hertting
G
G
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D004723:Endorphins / Q000502:physiology; D066298:In Vitro Techniques; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*
D004723:Endorphins; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017661:Receptors, Presynaptic; D000109:Acetylcholine; D004298:Dopamine