| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 University of Colorado Health Sciences Center, Denver, CO, USA
2 University of Texas Southwestern Medical Center, Dallas, TX, USA
* To whom correspondence should be addressed. E-mail: greg.fitz{at}utsouthwestern.edu.
The P2X family of ligand-gated cation channels is comprised of
seven distinct isoforms that are activated by binding of extracellular purines.
While originally identified in neurons, there is increasing evidence for expression
of P2X receptors in epithelia as well. Since ATP is released by both hepatocytes
and cholangiocytes, these studies were performed to evaluate whether P2X
receptors are present in cholangiocytes and contribute to local regulation of
biliary secretion and bile formation. RT-PCR of cDNA from cultured normal rat
cholangiocytes (NRCs) detected transcripts for P2X receptors 2, 3, 4 and 6;
products from P2X3 and P2X4 were robust and always detectable. In
chloangiocyte lysates, P2X4 protein was readily detected; and
immunohistochemical staining of intact rat liver revealed P2X4 protein
concentrated in intrahepatic bile ducts. To assess the functional significance of
P2X4, isolated Mz-ChA-1 cells were exposed to the P2X4-preferring agonist
2',3'-O-(4-benzoyl-benzoyl)-ATP (BzATP), which activated inward currents of -
18.2 + 3.0 pA/pF. In cholangiocyte monolayers, BzATP but not P2X3 agonists
elicited robust Cl- secretory responses (Isc) when applied to either the apical
(
Isc 22.1 ± 3.3 µA) or basolateral (18.5 ± 1.6 µA) chamber, with half-maximal
stimulation at ~10 µM and ~1 µM, respectively. The response to BzATP was
unaffected by suramin (NS), and was inhibited by Cu2+ (p<0.01). These studies
provide molecular and biochemical evidence for the presence of P2X receptors in
cholangiocytes. Functional studies indicate that P2X4 is likely to a primary
isoform involved, representing a novel and functionally important component of
the purinergic signaling complex modulating biliary secretion.
This article has been cited by other articles:
|
|
 |
|
  A. K. Dutta, K. Woo, R. B. Doctor, J. G. Fitz, and A. P. Feranchak Extracellular nucleotides stimulate Cl- currents in biliary epithelia through receptor-mediated IP3 and Ca2+ release Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1004 - G1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Woo, A. K. Dutta, V. Patel, C. Kresge, and A. P. Feranchak Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl- transport in biliary epithelial cells through a PKC{zeta}-dependent pathway J. Physiol., June 1, 2008; 586(11): 2779 - 2798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Kolachala, R. Bajaj, M. Chalasani, and S. V. Sitaraman Purinergic receptors in gastrointestinal inflammation Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G401 - G410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Qi, L. Chi, J. Faber, B. Koller, and A. J. Banes ATP reduces gel compaction in osteoblast-populated collagen gels J Appl Physiol, March 1, 2007; 102(3): 1152 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fausther, J. Lecka, F. Kukulski, S. A. Levesque, J. Pelletier, H. Zimmermann, J. A. Dranoff, and J. Sevigny Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8 Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G785 - G795. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
