title: Tachykinins protect cholinergic neurons from quinolinic acid excitotoxicity in striatal cultures.
abstract: The neuroprotective effect of tachykinins against excitotoxic death of cholinergic neurons was studied in rat striatal cell cultures. Quinolinic acid (QUIN) and kainic acid (KA) produced a dose dependent decrease in choline acetyltransferase activity, but KA was more potent. Our results show that substance P (SP) totally reversed the toxicity induced by 125 microM QUIN but not by 40 microM KA. This effect was also observed using protease inhibitors or a SP-analog resistant to degradation, [Sar9]-Substance P. The survival of neuron specific enolase- and acetylcholinesterase (AChE)-positive cells after treatment with QUIN alone or in the presence of SP was also examined. We observed that, while a decrease in total cell number produced by QUIN was not prevented by SP treatment, AChE-positive cells were rescued from the toxic damage. To characterize the SP protective effect we used more selective agonists of the three classes of neurokinin (NK) receptors. [Sar9, Met(O2)11]-Substance P (NK1 receptor agonist), [Nle10]-Neurokinin A (NK2 receptor agonist) or [Me-Phe7]-Neurokinin B (NK3 receptor agonist) were all able to block the toxic effect of QUIN on cholinergic activity. These results show that tachykinins provide an important protective support for striatal neurons, suggesting a possible therapeutical benefit in neurodegenerative disorders affecting cholinergic neurons.
authors.affiliation: Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Calvo
authors.forename: J
authors.initials: J
authors.lastname: Reiriz
authors.forename: E
authors.initials: E
authors.lastname: Pérez-Navarro
authors.forename: J
authors.initials: J
authors.lastname: Alberch
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D015320:Tachykinins; D017378:Quinolinic Acid