JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 24 June 2002. doi:10.1083/jcb.200204022
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 576K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cioffi, D. L.
Right arrow Articles by Stevens, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cioffi, D. L.
Right arrow Articles by Stevens, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2002/6/1267 $5.00
The Journal of Cell Biology, Volume 157, Number 7, June 24, 2002 1267-1278

Article

 Dominant regulation of interendothelial cell gap formation by calcium-inhibited type 6 adenylyl cyclase

Donna L. Cioffi1, Timothy M. Moore1, Jerry Schaack3, Judy R. Creighton1, Dermot M.F. Cooper2 and Troy Stevens1

1 Department of Pharmacology, University of South Alabama College of Medicine, Mobile, AL 36688
2 Departments of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262
3 Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262

Address correspondence to Troy Stevens, Department of Pharmacology, MSB 3364, University of South Alabama College of Medicine, Mobile, AL 36688. Tel.: (251) 460-6010. Fax: (251) 460-6798. E-mail: tstevens{at}jaguar1.usouthal.edu

Acute transitions in cytosolic calcium ([Ca2+]i) through store-operated calcium entry channels catalyze interendothelial cell gap formation that increases permeability. However, the rise in [Ca2+]i only disrupts barrier function in the absence of a rise in cAMP. Discovery that type 6 adenylyl cyclase (AC6; EC 4.6.6.1) is inhibited by calcium entry through store-operated calcium entry pathways provided a plausible explanation for how inflammatory [Ca2+]i mediators may decrease cAMP necessary for endothelial cell gap formation. [Ca2+]i mediators only modestly decrease global cAMP concentrations and thus, to date, the physiological role of AC6 is unresolved. Present studies used an adenoviral construct that expresses the calcium-stimulated AC8 to convert normal calcium inhibition into stimulation of cAMP, within physiologically relevant concentration ranges. Thrombin stimulated a dose-dependent [Ca2+]i rise in both pulmonary artery (PAECs) and microvascular (PMVEC) endothelial cells, and promoted intercellular gap formation in both cell types. In PAECs, gap formation was progressive over 2 h, whereas in PMVECs, gap formation was rapid (within 10 min) and gaps resealed within 2 h. Expression of AC8 resulted in a modest calcium stimulation of cAMP, which virtually abolished thrombin-induced gap formation in PMVECs. Findings provide the first direct evidence that calcium inhibition of AC6 is essential for endothelial gap formation.

Key Words: adenosine 3',5'-cyclic monophosphate; cAMP; store-operated calcium entry; thrombin; permeability


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents