Transient receptor potential vanilloid 1-mediated expression and secretion of endothelial cell-derived calcitonin gene-related peptide.
Calcitonin gene-related peptide (CGRP), the principal transmitter in sensory nerves, could also be expressed in vascular endothelium. Transient receptor potential vanilloid 1(TRPV1), which modulates the synthesis and release of CGRP in sensory nerves, is also present in endothelial cells. The present study tested whether TRPV1 modulates the release and synthesis of CGRP in endothelial cells, and evaluated the protective effect of endothelial cell-derived CGRP. Human umbilical vein endothelial cells (HUVECs) were treated with capsaicin or hyperthermia. The level of CGRP mRNA was detected by RT-PCR, and protein level was measured by radioimmunoassay. Endothelial cell injury was induced by lysophosphatidylcholine, and evaluated by cell viability and lactate dehydrogenase activity. HUVECs expressed CGRP, both alpha- and beta-subtype. Capsaicin increased the level of CGRP in the culture medium, and up-regulated the expression of CGRP in endothelial cells. Hyperthermia also increased the level of CGRP mRNA. These effects were abolished by capsazepine, a competitive antagonist of TRPV1. Capsaicin significantly attenuated the endothelial cell damage induced by LPC, which was prevented and aggravated by capsazepine or CGRP(8-37,) antagonist of CGRP receptor. These results indicate that TRPV1 also regulates the expression and secretion of endothelial cell-derived CGRP, which affords protective effects on endothelial cells.
Luo
Dan
D
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, China. dan962307@yahoo.com
Zhang
Yi-Wei
YW
Peng
Wei-Jie
WJ
Peng
Jun
J
Chen
Qing-Quan
QQ
Li
Dai
D
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005334:Fever; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D050916:TRPV Cation Channels / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D003470:Culture Media; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin