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- Title
Transcriptional Up-Regulation in Expression of 5-Hydroxytryptamine<sub>2A</sub> and Transcriptional Down-Regulation of Angiotensin II type 1 Receptors during Organ Culture of Rat Mesenteric Artery.
- Authors
Luo, Guogang; Xu, Cang-Bao; Cao, Yong-Xiao; Edvinsson, Lars
- Abstract
The purpose of this study was to investigate in rat mesenteric artery if there is up-regulation of 5-hydroxytryptamine (5-HT) receptors and angiotensin II receptors and the potential role of protein kinase C activation in the smooth muscle cells during organ culture. Angiotensin II, 5-HT and potassium induced contraction of ring segments without endothelium, monitored by a sensitivein vitropharmacology method. After the culture of the arterial ring segments for 24 hr, the concentration-contraction curves induced by 5-HT slightly shifted towards to the left with pEC50 from 6.64±0.11 to 6.84±0.11 and a significant increase in Emax from 147±11% to 246±15% (P<0.05), compared with that obtained in fresh segments. In contrast, the angiotensin II concentration-contraction curve only showed a significant decrease in Emax from 99±10% to 37±8%. Specific antagonists for the 5-HT type 2A receptors (5-HT2A) and angiotensin II type 1 receptors (AT1) demonstrated that the contractions occurred via 5-HT2A and AT1 receptors, respectively. Real-time PCR revealed that the 5-HT2A receptor mRNA was up-regulated in parallel with the contractile response while there was a down-regulation of AT1 receptor mRNA. Transcriptional inhibitor actinomycin D and specific protein kinase C inhibitor Ro31-8220 demonstrated that it was a transcriptional mechanism with involvement of protein kinase C that regulated the enhanced expression of 5-HT2A receptors in the mesenteric artery.
- Subjects
SEROTONIN; ANGIOTENSIN II; ANGIOTENSINS; ORGAN culture; TOXICOLOGY; PHARMACOLOGY; MEDICAL sciences
- Publication
Basic & Clinical Pharmacology & Toxicology, 2004, Vol 95, Issue 6, p280
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/j.1742-7843.2004.t01-1-pto950506.x