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: Potent sigma1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine modulates basal and N-methyl-D-aspartate-evoked nitric oxide production in vivo.
    Author: Bhardwaj A, Sawada M, London ED, Koehler RC, Traystman RJ, Kirsch JR.
    Journal: Stroke; 1998 Nov; 29(11):2404-10; discussion 2411. PubMed ID: 9804655.
    Abstract:
    BACKGROUND AND PURPOSE: final sigma-Receptor ligands ameliorate ischemic neuronal injury and modulate neuronal responses to N-methyl-D-aspartate (NMDA) receptor stimulation. Because NMDA-evoked synthesis of nitric oxide (NO) may play an important role in excitotoxic-mediated injury, we tested the hypothesis that final sigma-receptor ligands attenuate basal and NMDA-evoked NO production in the striatum in vivo. METHODS: Microdialysis probes were placed bilaterally into the striatum of halothane-anesthetized adult Wistar rats. Rats were divided into 7 treatment groups and perfused with artificial cerebrospinal fluid (aCSF) containing 3 micromol/L [14C]L-arginine for 2 to 3 hours followed by NMDA in various combinations with the following drugs: L-nitroarginine (L-NNA); the final sigma1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP); the selective final sigma1-receptor antagonist 1-(cyclopropylmethyl)-4-(2'-oxoethyl) piperidine hydrobromide (DuP 734); and the noncompetitive NMDA receptor blocker MK-801 in aCSF. Right-left differences between [14C]L-citrulline in the effluent from rats treated with different drug combinations were assumed to reflect differences in NO production. RESULTS: After a 3-hour loading period with [14C]L-arginine, addition of 1 mmol/L NMDA increased [14C]L-citrulline recovery compared with aCSF alone. This NMDA-evoked increase was inhibited by 1 mmol/L of L-NNA and PPBP. Perfusion of 1 mmol/L of the final sigma1-receptor antagonist DuP 734 with 1 mmol/L PPBP augmented NMDA-evoked [14C]L-citrulline recovery compared with perfusion with PPBP and NMDA. MK-801 attenuated the basal as well as NMDA-evoked [14C]L-citrulline recovery. PPBP did not cause any further attenuation in the basal and NMDA-evoked [14C]L-citrulline recovery in the presence of MK-801. CONCLUSIONS: These data indicate that a final sigma1-receptor ligand attenuates basal as well as NMDA-evoked NO production. Because the attenuated NO production was reversed by DuP 734, PPBP appears to act as an agonist at the final sigma1-receptor. Attenuated NO production by final sigma1-receptor agonists provides one possible mechanism for focal ischemic neuroprotection.
    [Abstract] [Full Text] [Related] [New Search]