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: [3H]ifenprodil binding to NMDA receptors in porcine hippocampal brain membranes.
    Author: Höfner G, Wanner KT.
    Journal: Eur J Pharmacol; 2000 Apr 14; 394(2-3):211-9. PubMed ID: 10771286.
    Abstract:
    (+/-)-2-(4-Benzylpiperidino)-1-(4-hydroxyphenyl)propan-1-ol ([3H]ifenprodil) binding to a subcellular fraction of porcine hippocampus, which was obtained by centrifugation on a discontinuous sucrose gradient, was investigated with the objective to label selectively the ifenprodil recognition site of native NMDA receptors. Saturation experiments revealed high-affinity sites for [3H]ifenprodil in this membrane fraction which could be characterised by a K(d) value of 23.0+/-1.8 nM using a one-site model. Calculation of saturation isotherms on the basis of a two-site model yielded a K(d1) value of 10.4+/-2.4 nM and a K(d2) value of 2200+/-1300 nM, respectively. Inhibition of [3H]ifenprodil binding by NR2B subunit-selective NMDA receptor antagonists, by polyamines, by sigma receptor ligands, by a variety of ligands acting at different NMDA receptor recognition sites and by several cations was studied and compared with the effects of these compounds on (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine ([3H]MK-801) binding under non-equilibrium conditions. It turned out that sigma receptor ligands such as 1, 3-di(2-tolyl)-guanidine (DTG), (+)-3-(3-hydroxyphenyl)-N-propylpiperidine (R)-3-PPP, (S)-3-PPP and (1-¿2-[bis(4-fluorophenyl)methoxy]ethyl¿)(-4-[3-phenylpropyl]piperazi ne) (GBR-12909) did not affect [3H]ifenprodil binding in the nanomolar range or only slightly. In contrast, ifenprodil, eliprodil, nylidrin and haloperidol inhibited [3H]ifenprodil binding in the nanomolar range and in the same rank order and with the same potency as observed for the inhibition of the high-affinity fraction of [3H]MK-801 binding. The polyamines, which activate NMDA receptors, inhibited [3H]ifenprodil binding in a biphasic manner. Their potency to inhibit the high-affinity fraction of [3H]ifenprodil binding was found to be in the same range as their potency to enhance [3H]MK-801 binding. In the presence of 10 microM spermine a significantly enhanced (P=0.0097) rate of dissociation of [3H]ifenprodil binding was found, suggesting that inhibition of [3H]ifenprodil binding by spermine is not, or at least not exclusively mediated by a competitive interaction.
    [Abstract] [Full Text] [Related] [New Search]