Academic Thesis

Basic information

Name Takeya Kosuke
Belonging department
Occupation name
researchmap researcher code 5000068922
researchmap agency Okayama University of Science

Title

Endothelin-1, but not angiotensin II, induces afferent arteriolar myosin diphosphorylation as a potential contributor to prolonged vasoconstriction

Bibliography Type

Joint Author

Author

Kosuke TAKEYA, Xuemei WANG, Iris KATHOL, Kathy LOUTZENHISER, Rodger LOUTZENHISER, Michael P WALSH.

Summary

Bolus administration of endothelin-1 elicits long-lasting renal afferent arteriolar vasoconstriction, in contrast to transient constriction induced by angiotensin II. Vasoconstriction is generally evoked by myosin regulatory light chain (LC20) phosphorylation at Ser19 by myosin light chain kinase (MLCK), which is enhanced by Rho-associated kinase (ROCK)-mediated inhibition of myosin light chain phosphatase (MLCP). LC20 can be diphosphorylated at Ser19 and Thr18, resulting in reduced rates of dephosphorylation and relaxation. Here we tested whether LC20 diphosphorylation contributes to sustained endothelin-1 but not transient angiotensin II-induced vasoconstriction. Endothelin-1 treatment of isolated arterioles elicited a concentration- and time-dependent increase in LC20 diphosphorylation at Thr18 and Ser19. Inhibition of MLCK or ROCK reduced endothelin-1-evoked LC20 mono- and diphosphorylation. Pretreatment with an ETB but not an ETA receptor antagonist abolished LC20 diphosphorylation, and an ETB receptor agonist induced LC20 diphosphorylation. In contrast, angiotensin II caused phosphorylation exclusively at Ser19. Thus, endothelin-1 and angiotensin ll induce afferent arteriolar constriction via LC20 phosphorylation at Ser19 due to calcium activation of MLCK and ROCK-mediated inhibition of MLCP. Endothelin-1, but not angiotensin H, induces phosphorylation of LC20 at Thr18. This could contribute to the prolonged vasoconstrictor response to endothelin-1.            

Magazine(name)

Kidney International

Publisher

Volume

2

Number Of Pages

StartingPage

370

EndingPage

381

Date of Issue

2015/02

Referee

Exist

Invited

Language

English

Thesis Type

Research papers (academic journals)

ISSN

DOI

10.1038/ki.2014.284

NAID

PMID

25140913

URL

J-GLOBAL ID

arXiv ID

ORCID Put Code

DBLP ID