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Divergent effects of corticotropin releasing hormone on endothelial cell nitric oxide synthase are associated with different expression of CRH type 1 and 2 receptors
Author(s) -
Cantarella Giuseppina,
Lempereur Laurence,
Lombardo Gabriella,
Chiarenza Andrea,
Pafumi Carlo,
Zappalà Giovanna,
Bernardini Renato
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704322
Subject(s) - receptor , corticotropin releasing hormone , medicine , inflammation , endocrinology , cytokine , endothelial stem cell , nitric oxide synthase , endothelium , nitric oxide , biology , chemistry , in vitro , biochemistry
Endothelium is a target for an array of factors involved in inflammation. Endothelial cells express receptors for CRH, a neuropeptide produced during inflammation. We report both the concentration‐dependent inhibitory effect of CRH upon cytokine‐stimulated nitrite release by H5V murine endothelioma cells, and its stimulatory one in HUVEC cells. Western blot analysis showed that CRH inhibits cytokine‐stimulated iNOS protein in H5V cells, and, instead, potentiated it in HUVEC cells. H5V cells expressed both CRH receptors (CRH‐R1 and R2) mRNAs, whereas HUVEC cells expressed the CRH‐R2 mRNA solely. CRH increased medium nitrites and iNOS protein expression in H5V cells pretreated with the selective CRH‐R1 antagonist CP 154,526. However, the selective CRH‐R2 antagonist anti‐Svg‐30 failed to produce similar effects. In fact, anti‐Svg‐30 inhibited CRH‐induced increase of nitrite release and iNOS expression in HUVEC cells. Our results confirm the activating role of CRH on endothelial cells, although it suggests its possible inhibitory role in the late phase of the inflammatory response. NO‐mediated effects of CRH on endothelial cells could be exploited in therapeutic strategies related to inflammatory and/or degenerative diseases.British Journal of Pharmacology (2001) 134 , 837–844; doi: 10.1038/sj.bjp.0704322