Endogenous dopamine release from tuberoinfundibular neurons: does calmodulin play any role?
The possible involvement of calmodulin in the process of endogenous dopamine (DA) release from arcuate-periventricular nuclei-median eminence fragments, containing tuberoinfundibular dopaminergic (TIDA) neurons, has been investigated in an in vitro incubation system. For this purpose the basal and K+-stimulated DA release was examined in the presence and in the absence of the different putative calmodulin antagonists, pimozide, trifluoperazine, penfluridol and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). Trifluoperazine and pimozide in concentrations up to 100 microM were both uneffective in blocking K+-evoked DA release. Penfluridol in doses of 5 and 10 microM, did not prevent 35 mM K+-induced endogenous DA release. It was able to reduce K+-stimulated DA release only at the very large concentration of 100 microM. W-7 added in vitro to the hypothalamic fragments, prevented endogenous DA release evoked by 35 mM K+ in a dose-dependent manner. W-5, a chlorine deficient analogue of W-7, that interacts only weakly with calmodulin, failed to modify K+-stimulated endogenous DA release in doses up to 200 microM. All the putative calmodulin antagonists used in the present study did not induce any change of basal DA release. In conclusion the fact that most of the agents, except W-7, known to antagonize calmodulin-dependent processes in many biological systems failed to interfere with the release of endogenous DA from TIDA neurons seems to suggest that calmodulin does not play a crucial role in the process of DA release and that the inhibitory effect of W-7 on endogenous DA release may be better attributed to other mechanisms different from its anticalmodulin action.
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D010868:Pimozide / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; D010868:Pimozide; D014268:Trifluoperazine; C017967:W 7; D011188:Potassium; D004298:Dopamine