Morphine-mediated alteration of hypertension-related gene expression in human white blood cells and multilineage progenitor cells

作者：Banach M; Casares F M; Kream R M; Gluba A; Rysz J; Stefano G B^*

来源：Journal of Human Hypertension, 2010, 24(11): 713-720.

DOI：10.1038/jhh.2010.69

• endogenous morphine
• mu3 opiate receptor
• endothelial cells
• human stem cells
• human white blood cells
• nitric oxide

It has been shown that vascular endothelial cells functionally express a local circuit autocrine-paracrine regulatory pathway driven by endogenously expressed chemically authentic morphine, its cognate opiate alkaloid-selective mu3 and mu4 receptors, and constitutive nitric oxide (NO). Accordingly, the aim of the study was to examine morphine-mediated changes in hypertension-associated gene expression in two independent cell models: primary cultures of human white blood cells (WBCs) and human multilineage progenitor cells (MLPCs). In separate incubations, primary cultures of human WBC and MLPC were treated with morphine at a final concentration of 1 mu M morphine for 2-4 h. After RNA extraction and reverse transcription, Human Genome Survey Arrays were used to construct and differentially analyze by strict statistical criteria transcriptional/gene expression profiles of WBC and undifferentiated human MLPC in three independent experiments. The Applied Biosystems Human Genome Survey Array contains 31 700 60-mer oligonucleotide probes representing a set of 27 868 individual human genes and > 1000 control probes. After DNA microarray analyses, a variety of hypertension-associated genes from both cell types were observed to be significantly downregulated. The only genes expressed in both cell types were beta-adrenergic receptor kinase 2 (ADRBK2) and coding protein kinase WNK1 (PRKWNK1); however, only PRKWNK1 showed downregulation of its expression after morphine exposure. Only two genes were observed to be significantly upregulated after morphine treatment: ADRBK2 in stem cells and beta 3-adrenergic receptor in WBC. Morphine administration to primary cultures of human WBC and MLPC altered the expression profile of 16 candidate hypertension-associated genes. The majority of relevant genes was observed to be downregulated, suggesting ongoing homeostatic regulation by endogenous morphine coupled to NO production and release. In sum, these data suggest a predominantly antihypertensive role for endogenous morphine/NO signaling events. Journal of Human Hypertension (2010) 24, 713-720; doi:10.1038/jhh.2010.69; published online 8 July 2010

• 出版日期2010-11