Clonidine induces calcitonin gene-related peptide expression via nitric oxide pathway in endothelial cells.
The present study was to determine whether clonidine could induce calcitonin gene-related peptide (CGRP) production and the underlying mechanisms. Human umbilical vein endothelial cells were treated with clonidine and the dose-effect or time-effect relationship of clonidine on CGRP production was examined. Yohimbine (a alpha(2)-adrenoceptor blocker) and L-NAME (an antagonist of nitric oxide synthase, NOS) were chosen to explore the role of alpha(2)-adrenoceptor and nitric oxide pathway in the effect of clonidine on endothelial cell-derived CGRP production. The level of CGRP mRNA or protein was detected by Real Time-PCR or radioimmunoassay. Nitric oxide content was measured by nitroreduction assay. The study showed that clonidine was able to induce CGRP mRNA (alpha- and beta-isoforms) expression in a dose-dependent manner in endothelial cells. The effect of clonidine on endothelial cell-derived CGRP synthesis and secretion was attenuated in the presence of yohimbine. L-NAME treatment could also inhibit clonidine-induced CGRP synthesis and secretion concomitantly with the decreased NO content in culture medium. These results suggest that clonidine could stimulate CGRP synthesis and secretion in endothelial cells through the activation of alpha(2)-adrenoceptor, which is related to the NO pathway.
Zhang
Yi-Min
YM
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, 110 Xiang-Ya Road, Changsha, Hunan, China.
Peng
Jun
J
Hu
Chang-Ping
CP
Jiang
Qiu-Tao
QT
Jiang
Guo-Long
GL
Li
Yuan-Jian
YJ
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester