Tissue-specific patterns of neurokinin-1 receptor (NK-1R) gene expression in mice exposed to sidestream cigarette smoke.

Abstract

Neurokinin-1 receptor (NK-1R), a high-affinity plasma membrane-bound receptor for neurokinin substance P, plays important roles in the onset of the pathophysiological responses. To test whether the transcript levels of gene encoding NK-1R in organs are affected by sidestream cigarette smoke (SSCS) exposure, the C57BL/6 mice were randomly assigned to five groups (six/group) in a study of the dose-effect relationship. The mice were exposed to 0 (filtered room air), 2, 4, 8 and 16 mg total particulate matter (TPM) of SSCS/exposure/day, respectively, for seven days through a nose-only exposure chamber (IN-TOX, Albuquerque, NM, USA). The levels of NK-1R mRNA in the lung, heart, liver, kidney and spleen tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) techniques and normalized against GAPDH expression. NK-1R mRNA in heart tissue showed SSCS-induced dose-dependent downregulation, with minimum expression at a dose of 8.0 mg TPM. Whereas, the levels of NK-1R mRNA in the liver were upregulated to 2.86 and 5.13-fold after exposure to 2.0 and 4.0 mg TPM of SSCS respectively, then returned to 4.19 and 3.93-fold at the exposure doses of 8.0 and 16.0 mg TPM, respectively, when compared to that of the control. In the kidney, SSCS exposure at a dose of 2.0 TPM, but not higher than that level, induced significant elevation of NK-1R mRNA expression. These findings suggest that there are the paracrine and/or autocrine signalling mechanisms through receptor-ligand interactions. No alteration of NK-1R gene expression was observed in the lungs and spleen tissues in this study. The tissue-specific patterns by which SSCS affect NK-1R gene expression in these organs may partially explain dissimilarity of NK-1R activation and the associated toxicity caused by environmental tobacco smoke.