| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Tufts University School of Medicine, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: iarias{at}helix.nih.gov.
Bile acid secretion induced by cAMP and taurocholate is associated with recruitment of several ATP Binding Cassette (ABC) transporters to the canalicular membrane. Taurocholate-mediated bile acid secretion and recruitment of ABC transporters are PI 3-kinase dependent and require an intact microtubular apparatus. We examined mechanisms involved in cAMP-mediated bile acid secretion. Bile acid secretion induced by perfusion of rat liver with dBcAMP was blocked by colchicine and Wortmannin, a PI 3-kinase inhibitor. Canalicular membrane vesicles isolated from cAMP-treated rats manifested increased ATP-dependent transport of taurocholate and PI 3-kinase activity which were reduced by prior in vivo administration of colchicine or Wortmannin. Addition of PI 3-kinase lipid product, PI 3,4-P2, but not its isomer, PI 4,5-P2, restored ATP-dependent taurocholate in these vesicles. Addition of a decapeptide, which activates PI 3-kinase, to canalicular membrane vesicles increased ATP-dependent transport above baseline activity. In contrast to effects induced by taurocholate, cAMP-stimulated intracellular trafficking of the canalicular ABC transporters was unaffected by Wortmannin and recruitment of mrp2, but not bsep, was partially decreased by colchicine. These studies indicate that trafficking of bsep and other canalicular ABC transporters to the canalicular membrane in response to cAMP is independent of PI 3-kinase activity. In addition, PI 3-kinase lipid products are required for activation of bsep in the canalicular membrane. These observations prompt revision of current concepts regarding the role of cAMP and PI 3-kinase in intracellular trafficking, regulation of canalicular bsep and bile acid secretion.
This article has been cited by other articles:
|
|
 |
|
  T. Kagawa, N. Watanabe, K. Mochizuki, A. Numari, Y. Ikeno, J. Itoh, H. Tanaka, I. M. Arias, and T. Mine Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G58 - G67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mochizuki, T. Kagawa, A. Numari, M. J. Harris, J. Itoh, N. Watanabe, T. Mine, and I. M. Arias Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G818 - G828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Mottino, F. A. Crocenzi, E. J. S. Pozzi, L. M. Veggi, M. G. Roma, and M. Vore Role of microtubules in estradiol-17{beta}-D-glucuronide-induced alteration of canalicular Mrp2 localization and activity Am J Physiol Gastrointest Liver Physiol, February 1, 2005; 288(2): G327 - G336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Cullen, J. McCool, M. S. Anwer, and C. R. L. Webster Activation of cAMP-guanine exchange factor confers PKA-independent protection from hepatocyte apoptosis Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G334 - G343. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
