[Effects of dynorphin A1-17 on the activities, immunoreactivities and mRNA expression of cNOS and iNOS in rat spinal cord and their mechanisms].
Intrathecal administration(i.t.) of Dynorphin A1-17(Dyn) 1.25-20 nmol produced dose-dependent paralysis of hindlimbs and tail as well as inhibition of tail flick and foot flinch reflexes. The Dyn spinal neurotoxicity and antinociception involve two differential mechanisms: Enhancement of NMDA-Ca(2+)-NOS/NO pathway and c-fos over-expression in the ventral spinal cord for neurotoxicity, and depression of NMDA receptor and NOS activities in the dorsal spinal cord for antinociception. Both brain-derived constitutive NOS (predominant at early stage) and inducible NOS (at later stage) are detrimental, but endothelial constitutive NOS might be beneficial to Dyn spinal neurotoxicity. Dyn exerts a dualistic modulatory effect on [Ca2+]i of the cultured rat single spinal neurons, inducing sustained overload of intracellular free calcium via both NMDA and kappa receptor activation at higher concentrations, and producing significant inhibition of the depolarization-evoked calcium influx only via kappa receptor activation at lower concentrations. Dyn exposure for 1 h produced direct neurotoxicity in the cultured spinal neurons within an optimal range of concentrations.
Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, Beijing.
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D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism
D000700:Analgesics; D012333:RNA, Messenger; D004399:Dynorphins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat