These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Preferential inhibition by a novel Na(+)/Ca(2+) channel blocker NS-7 of severe to mild hypoxic injury in rat cerebrocortical slices: A possible involvement of a highly voltage-dependent blockade of Ca(2+) channel.
    Author: Oka M, Itoh Y, Ukai Y.
    Journal: J Pharmacol Exp Ther; 2000 May; 293(2):522-9. PubMed ID: 10773024.
    Abstract:
    The hypoxic injury was induced in rat cerebrocortical slices by the exposure to hypoxia for 45 min in the absence or presence of 3 mM glucose, followed by reoxygenation for 5 h. The injury was more pronounced in the absence of glucose (severe hypoxic injury) than in the presence of glucose (mild hypoxic injury). A novel Na(+)/Ca(2+) channel blocker, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], at 3 to 30 microM inhibited preferentially the severe hypoxic injury, whereas MK-801, omega-conotoxin GVIA (omega-CTX), and N(G)-nitro-L-arginine methylester suppressed preferentially the mild hypoxic injury. The extracellular cyclic GMP formation, a marker of nitric oxide synthesis, was enhanced during hypoxia, although the extent was greater in the absence of glucose. As observed in the hypoxic injury, NS-7 preferentially inhibited the cyclic GMP formation induced by severe hypoxic insults, whereas MK-801 or omega-CTX reduced it under mild hypoxic condition. When 30 to 50 mM KCl was applied to normoxic slices, a concentration-dependent increase in the extracellular cyclic GMP formation was observed. NS-7 blocked the cyclic GMP formation induced by 50 mM KCl but not by 30 to 40 mM KCl, whereas omega-CTX suppressed only the 30 mM KCl-evoked response. In primary neuronal culture, NS-7 reversed KCl-induced increase in intracellular Ca(2+) in which the inhibition was marked when the KCl concentration was increased. These findings suggest that NS-7, unlike other neuroprotective compounds used in this study, is more effective in severe hypoxic injury. The highly voltage-dependent Ca(2+) channel blockade may contribute to the mode of neuroprotective action of NS-7.
    [Abstract] [Full Text] [Related] [New Search]