Premium
Transcriptional Up‐Regulation in Expression of 5‐Hydroxytryptamine 2A and Transcriptional Down‐Regulation of Angiotensin II type 1 Receptors during Organ Culture of Rat Mesenteric Artery
Author(s) -
Luo Guogang,
Xu CangBao,
Cao YongXiao,
Edvinsson Lars
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.t01-1-pto950506.x
Subject(s) - receptor , angiotensin ii , contraction (grammar) , medicine , endocrinology , angiotensin receptor , 5 ht receptor , vascular smooth muscle , biology , mesenteric arteries , serotonin , chemistry , microbiology and biotechnology , artery , smooth muscle
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 sensitive in vitro pharmacology 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 pEC 50 from 6.64±0.11 to 6.84±0.11 and a significant increase in E max 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 E max from 99±10% to 37±8%. Specific antagonists for the 5‐HT type 2A receptors (5‐HT 2A ) and angiotensin II type 1 receptors (AT 1 ) demonstrated that the contractions occurred via 5‐HT 2A and AT 1 receptors, respectively. Real‐time PCR revealed that the 5‐HT 2A receptor mRNA was up‐regulated in parallel with the contractile response while there was a down‐regulation of AT 1 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‐HT 2A receptors in the mesenteric artery.