Evidence for modulatory effects of substance P fragments (1-4) and (8-11) on endogenous dopamine outflow in rat striatal slices.
The effects of substance P-(1-4) and substance P-(8-11) on endogenous dopamine outflow in rat striatal slices were investigated. The dose-response curves (0.01 nM to 1 microM) were bell-shaped for both peptides, with significant increases in dopamine outflow at 0.1 and 1 nM. Dopamine overflow elicited by 1 nM substance P-(1-4) or substance P-(8-11) and 25 mM KCl was additive. Although substance P-(8-11) contains a truncated tachykinin sequence, the tachykinin NK1 receptor antagonist WIN 51,708 (17 beta-hydroxy-17 alpha-ethynyl-5 alpha-androstano[3,2-b]pyrimido[1,2- a]benzimidazole (2.5 nM) fully reversed its effect. The interaction between the antagonist and 1 nM substance P-(1-4) was statistically not significant. The data constitute the first evidence that the fragments substance P-(1-4) and substance P-(8-11) could exert central effects and suggest that they may play a role in neuromodulation in the basal ganglia.
Khan
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Department of Pharmacology, Queen Mary and Westfield College, London, UK.
Whelpton
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Michael-Titus
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D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology*
D000731:Androstanes; D001562:Benzimidazoles; C086111:WIN 51708; D013373:Substance P; D004298:Dopamine