Lipid soluble smoke particles upregulate endothelin receptors in rat basilar artery.
The present study examines the effect of dimethylsulphoxide-soluble particles (DSP) from cigarette smoke on endothelin (ET) receptors in the basilar artery. The contractile responses to ET-1 (ET(A) and ET(B) receptors agonist) and sarafotoxin 6c (ET(B) receptor agonist) were studied using a sensitive myograph. The mRNA levels of ET receptors were determined with real-time PCR, while the protein level was evaluated by immunohistochemistry. The results showed that a DSP concentration of 0.4 microl/ml increased the contractile responses induced by sarafotoxin 6c and ET-1 and the mRNA and protein levels of the ET receptors. Inhibitor SB203580 (a p38 inhibitor), staurosporine (a PKC inhibitor) or wedelolactone (a NF-kappaB inhibitor) attenuated the elevated sarafotoxin 6c-induced contraction, the increased mRNA expression and protein levels of the ET(B) receptor induced by DSP. The effects on the ET(A) receptor induced by DSP 0.4 microl/ml were inhibited by co-incubation with PD98059 (an ERK1/2 inhibitor) or SP600125 (a JNK inhibitor) and were further enhanced by SB203580. The results indicate that DSP 0.4 microl/ml upregulates the ET(B) receptor of basilar arterial smooth muscle cells via activation of the p38 pathway and transcriptional factor NF-kappaB, while also upregulating the ET(A) receptor via activation of the ERK1/2 and JNK pathways. Additionally, the p38 pathway seems to be involved in the feedback regulation of the ET(A) receptor.
Huang
Lin-Hong
LH
Department of Pharmacology, Xi'an Jiaotong University College of Medicine, and Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
He
Jian-Yu
JY
Yuan
Bing-Xiang
BX
Cao
Yong-Xiao
YX
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D004121:Dimethyl Sulfoxide; D005260:Female; D005786:Gene Expression Regulation; D008055:Lipids / Q000737:chemistry*; D008297:Male; D052638:Particulate Matter; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism*; D012906:Smoke; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects; D014757:Viper Venoms
D008055:Lipids; D052638:Particulate Matter; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D012906:Smoke; D014757:Viper Venoms; C057354:sarafotoxins s6; D004121:Dimethyl Sulfoxide