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Relationship between PDK1 and contraction in carotid arteries in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model

We studied the relationship between 3-phosphoinositide-dependent protein kinase 1 (PDK1) and contractions induced by serotonin, phenylephrine, and thromboxane A 2 mimetic (U46619) in the presence of nitric oxide synthase inhibitor in the carotid arteries of Goto-Kakizaki (GK) rats, a spontaneous typ...

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Published in:Canadian journal of physiology and pharmacology 2017-04, Vol.95 (4), p.459-462
Main Authors: Watanabe, Shun, Matsumoto, Takayuki, Taguchi, Kumiko, Kobayashi, Tsuneo
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description We studied the relationship between 3-phosphoinositide-dependent protein kinase 1 (PDK1) and contractions induced by serotonin, phenylephrine, and thromboxane A 2 mimetic (U46619) in the presence of nitric oxide synthase inhibitor in the carotid arteries of Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, in the chronic stage of disease. Serotonin-induced contraction was greater in the GK rats than in the control Wistar rats. A specific PDK1 inhibitor (GSK2334470) decreased the serotonin-induced contraction in the GK rats but not in the Wistar rats, and the difference in such contraction was abolished with this treatment. In GK rats, phenylephrine-induced contraction exhibited a leftward shift and U46619-induced contraction was greater still. Phenylephrine- and U46619-induced contractions were reduced by GSK2334470 in both groups. These results suggest, for the first time, that the contribution of PDK1 is different among 3 vasoconstrictors and that PDK1 contributed to increased serotonin-induced contraction in the carotid arteries of GK rats.
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Serotonin-induced contraction was greater in the GK rats than in the control Wistar rats. A specific PDK1 inhibitor (GSK2334470) decreased the serotonin-induced contraction in the GK rats but not in the Wistar rats, and the difference in such contraction was abolished with this treatment. In GK rats, phenylephrine-induced contraction exhibited a leftward shift and U46619-induced contraction was greater still. Phenylephrine- and U46619-induced contractions were reduced by GSK2334470 in both groups. 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subjects 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology
3-Phosphoinositide-Dependent Protein Kinases - antagonists & inhibitors
3-Phosphoinositide-Dependent Protein Kinases - metabolism
Animals
artère carotide
Carotid arteries
Carotid Arteries - drug effects
Carotid Arteries - physiology
carotid artery
Chronic Disease
contraction
Diabetes
Diabetes Mellitus, Type 2 - complications
Diabetic Angiopathies - drug therapy
Diabetic Angiopathies - etiology
Diabetic Angiopathies - metabolism
diabète de type 2
Disease Models, Animal
GK rat
Health aspects
Indazoles - pharmacology
Kinases
Male
Nitric Oxide - metabolism
Nitric Oxide Synthase - antagonists & inhibitors
PDK1
Phenylephrine - pharmacology
Protein kinases
Pyrimidines - pharmacology
rat GK
Rats
Rats, Wistar
Rodents
Serotonin
Serotonin - pharmacology
Signal Transduction
Thromboxane A2 - analogs & derivatives
Type 2 diabetes
Vasoconstriction - drug effects
Vasoconstrictor Agents - pharmacology
title Relationship between PDK1 and contraction in carotid arteries in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model
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