Insulin modulation of cloned mouse NMDA receptor currents in Xenopus oocytes.
Modulation of recombinant N-methyl-D-aspartate receptor (NMDAR) currents by insulin was studied using the Xenopus oocyte expression system. Insulin (0.8 microM, 10 min) regulated NMDAR currents in a subunit-specific manner. Currents from epsilon1/zeta1, epsilon2/zeta1, and epsilon4/zeta1 receptors were variably potentiated, whereas currents from epsilon3/zeta1 receptors were not. Protein tyrosine kinases (PTKs) and protein kinase C were found to be involved in insulin-mediated modulation in an NMDAR subtype-specific way. Pretreatment with a specific PTK inhibitor, lavendustin A, attenuated and blocked the insulin effect on epsilon2/zeta1 and epsilon4/zeta1, respectively. Preincubation with selective protein kinase C inhibitors, staurosporine or calphostin C, depressed the response of epsilon1/zeta1 and epsilon2/zeta1 receptors to insulin. Basal regulation of NMDAR currents by endogenous PTKs and protein tyrosine phosphatases (PTPs) was also investigated. Of the four receptor subtypes, only epsilon1/zeta1 receptor currents were affected by basal PTK inhibition via lavendustin A, whereas PTP inhibition by phenylarsine oxide or orthovanadate enhanced currents from epsilon1/zeta1 and epsilon2/zeta1 receptors. Surprisingly, a stimulatory PTP modulation was observed for epsilon4/zeta1. As NMDAR subunits are differentially expressed in the brain, the observed subtype-specific modulations of NMDAR currents by insulin, PTKs, and PTPs may provide important insights into certain NMDAR-dependent physiological and pathological processes.
Liao
G Y
GY
Department of Biological Sciences, University of Illinois at Chicago, 60607, USA.
Leonard
J P
JP
D000818:Animals; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014982:Xenopus laevis; D062368:meta-Aminobenzoates
D004791:Enzyme Inhibitors; D007328:Insulin; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D012459:Salicylates; D062368:meta-Aminobenzoates; C092428:lavendustin B; D015240:Phorbol 12,13-Dibutyrate; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine