5-HT2 receptor regulation of acetylcholine release induced by dopaminergic stimulation in rat striatal slices.
The role of 5-hydroxytryptamine (5-HT) receptor subtypes in acetylcholine (ACh) release induced by dopamine or neurokinin receptor stimulation was studied in rat striatal slices. The dopamine D1 receptor agonist SKF 38393 potentiated in a tetrodotoxin-sensitive manner the K(+)-evoked [3H]ACh release while SCH 23390, a dopamine D1 receptor antagonist, had no effect. [3H]ACh release was decreased by the dopamine D2 receptor agonist LY 171555 (quinpirole) and slightly potentiated by the dopamine D2 receptor antagonist haloperidol. The selective neurokinin NK1 receptor agonist [Sar9, met(O2)11]SP also potentiated K(+)-evoked release of [3H]ACh. GR 82334, a NK1 receptor antagonist, blocked not only the effect of [Sar9, met(O2)11]SP but also the release of ACh induced by the D1 receptor agonist SKF 38393. Among the 5-HT agents studied, only the 5-HT2A receptor antagonists ketanserin and ritanserin were able to reduce the ACh release induced by dopamine D1 receptor stimulation. Mesulergine, a more selective 5-HT2C antagonist, showed an intrinsic releasing effect but did not affect K(+)-evoked ACh release induced by SKF 38393. Methysergide and methiothepin, mixed 5-HT1/2 antagonists, as well as ondansetron, a 5-HT3 receptor antagonist, showed an intrinsic effect on ACh release, their effects being additive to that of SKF 38393. 5-HT2 receptor agonists were ineffective. However, the 5-HT2 agonist DOI was able to prevent the antagonism by ketanserin of the increased [3H]ACh efflux elicited by SKF 38393, suggesting a permissive role of 5-HT2A receptors. None of the above indicated 5-HT agents was able to reduce the ACh release induced by the selective NK1 agonist. The results suggest that 5-HT2 receptors, probably of the 5-HT2A subtype, modulate the release of ACh observed in slices from the rat striatum after stimulation of dopamine D1 receptors. It seems that this serotonergic control is exerted on the interposed collaterals of substance P-containing neurons which promote ACh efflux through activation of NK1 receptors located on cholinergic interneurons.
Ramírez
M J
MJ
Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.
Cenarruzabeitia
E
E
Lasheras
B
B
Del Rio
J
J
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010803:Physalaemin / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C054724:senktide; C079014:GR 82334; D016713:Ritanserin; D010803:Physalaemin; D013373:Substance P; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D007650:Ketanserin; D006220:Haloperidol; D000109:Acetylcholine; D011188:Potassium; C031649:mesulergine