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Mechanisms underlying increased serotonin-induced contraction in carotid arteries from chronic type 2 diabetic Goto-Kakizaki rats.
MedLine Citation:
PMID:  25034165     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Serotonin (5-hydroxytryptamine: 5-HT) plays important roles in the cardiovascular system; however, the relationship between 5-HT-induced vasocontraction and the arterial 5-HT system including metabolism and signal transduction, in the presence of chronic type 2 diabetes (T2D) remains unclear. Therefore, we investigated 5-HT-induced contraction and associated mechanisms in carotid arteries from chronic T2D Goto-Kakizaki (GK) rats. Contractions in response to 5-HT were examined in carotid arteries from GK rats (42-46 weeks old). To investigate the response mechanisms of arterial smooth muscle, we constructed concentration-response curves for TCB2 (5-HT2A-receptor agonist), BW723C86 (5-HT2B-receptor agonist), and 5-HT in the presence of various inhibitors using endothelium-denuded preparations. Carotid arterial expressions of monoamine oxidase-A (MAO-A), serotonin transporter (SERT), and 5-HT2A were detected by immunoblotting. 5-HT-induced contraction was increased in carotid arteries from GK compared to control Wistar rats in both endothelium-intact and -denuded preparations. In denuded preparations, we found that: 1) TCB2-induced contraction was increased in GK rat arteries (vs. Wistar); 2) MAO-A inhibitor did not affect 5-HT-induced contraction, whereas SERT inhibitor augmented such contractions in both groups; and 3) differences in 5-HT-induced contractions were abolished by p38 MAPK, PI3K, and Rho kinase inhibitors. Carotid arterial expressions of MAO-A, SERT, and 5-HT2A remained unchanged in the groups. The results suggest that 5-HT-induced contraction is augmented in T2D GK rat carotid arteries. This augmentation is due to smooth muscle activation partly mediated by p38 MAPK, PI3K, and Rho kinases, and may also be partly due to arterial SERT activity.
Authors:
Takayuki Matsumoto; Shun Watanabe; Kumiko Taguchi; Tsuneo Kobayashi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-14
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  -     ISSN:  1096-1186     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ltd.
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