Facilitation of striatal acetylcholine release by dopamine D1 receptor stimulation: involvement of enhanced nitric oxide production via neurokinin-2 receptor activation.
The regulation of striatal cholinergic function by dopamine D1 receptor activation was examined in vivo in urethane-anaesthetized rats with microdialysis probes. Extracellular acetylcholine levels were enhanced by activation of D1 receptors either directly by a striatal application of the D1 receptor agonist (+)-SKF-38393 (3 microM) or indirectly by the release of dopamine evoked by striatal application of neurotensin (0.1 microM) under D2 receptor blockade. SR 144190, a new potent and selective non-peptide neurokinin-2 receptor antagonist (0.03-1 mg/kg, i.p.), dose-dependently reduced the acetylcholine release induced by (+)-SKF-38393 or neurotensin. Furthermore, intrastriatal application of SR 144190 (1 nM) blocked the increase in acetylcholine release induced by the local application of (+)-SKF-38393 (3 microM), neurokinin A (1 microM) or substance P (1 microM). Finally, a role for nitric oxide in mediating the effects of D1 neurokinin-2 receptor activation on acetylcholine release is proposed since local infusion of the competitive inhibitor of nitric oxide synthase, N(G)-monomethyl-L-arginine (0.01-10 microM), blocked the increase in acetylcholine release induced by (+)-SKF-38393 (3 microM), neurotensin (0.1 microM) or neurokinin A (1 microM) without affecting the enhancing effect of the neurokinin-1 agonist septide (0.1 microM).
Steinberg
R
R
Sanofi Recherche, Neuropsychiatry Department, Montpellier, France.
Souilhac
J
J
Rodier
D
D
Alonso
R
R
Emonds-Alt
X
X
Le Fur
G
G
Soubrié
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008782:Methylurea Compounds / Q000494:pharmacology; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D065127:Dopamine D2 Receptor Antagonists; D004791:Enzyme Inhibitors; D008782:Methylurea Compounds; D009025:Morpholines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018041:Receptors, Neurokinin-2; C110304:SR 144190; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009496:Neurotensin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine