ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : Modulation of recombinant N-methyl-d-aspartate receptor (NMDAR) currents by insulin was studied using the Xenopus oocyte expression system. Insulin (0.8 μM, 10 min) regulated NMDAR currents in a subunit-specific manner. Currents from ε1/ξ1, ε2/ξ1, and ε4/ξ1 receptors were variably potentiated, whereas currents from ε3/ξ1 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 ε2/ξ1 and ε4/ξ1, respectively. Preincubation with selective protein kinase C inhibitors, staurosporine or calphostin C, depressed the response of ε1/ξ1 and ε2/ξ1 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 ε1/ξ1 receptor currents were affected by basal PTK inhibition via lavendustin A, whereas PTP inhibition by phenylarsine oxide or orthovanadate enhanced currents from ε1/ξ1 and ε2/ξ1 receptors. Surprisingly, a stimulatory PTP modulation was observed for ε4/ξ1. 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0731510.x
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