Published ahead of print on July 10, 2003, doi:10.1165/rcmb.2003-0177OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 2, February 2004, 139-144 A more recent version of this article appeared on February 1, 2004
Submitted on May 6, 2003 Ionotropic glutamate receptors in lungs and airways: molecular basis for glutamate toxicityKathleen G Dickman1,1 VA Medical Center, Northport, N.Y., USA; Medicine, SUNY at Stony Brook, Stony Brook, N.Y., USA, 2 Medicine, SUNY at Stony Brook, Stony Brook, N.Y., USA, 3 VA Medical Center, Northport, N.Y., USA * To whom correspondence should be addressed. E-mail: ssaid{at}notes.cc.sunysb.edu.
We earlier showed that the ionotropic glutamate receptor agonist NMDA induces excitotoxic pulmonary edema, and that endogenous activation of NMDA receptors (NMDAR) could mediate lung injury caused by oxidative stress. In this study, we searched for evidence of NMDAR expression in the rat lung and in the alveolar macrophage (AM) cell line NR8383, and for possible regulation of receptor expression by NMDA. The presence of mRNA for NMDAR 1 and the 4 known NMDAR 2 subtypes (A, B, C, and D) was examined by RT-PCR using isoform-specific primers. NMDAR 1 was expressed in all lung regions examined (peripheral, mid-lung, and mainstem), as well as in trachea and the AMs. Expression of NMDAR 2A and 2B subtypes was not detected, while NMDAR 2C was present only in peripheral and mid-lung samples. NMDAR 2D was the dominant subtype expressed in the peripheral, gas-exchange zone of lung and in alveolar macrophages, and this expression was upregulated in lungs treated with NMDA. Western blot confirmed the presence of NMDAR 1 protein in all lung regions and in AMs. These findings provide a molecular-biological basis for the excitotoxic actions of glutamate in rat lungs and airways, and raise the question of a possible physiological role for NMDA receptors in lung and airway function.
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