title: Ion transport regulation by P2Y receptors, protein kinase C and phosphatidylinositol 3-kinase within the semicircular canal duct epithelium.
abstract: BACKGROUND
  The ionic composition of the luminal fluid in the vestibular labyrinth is maintained within tight limits by the many types of epithelial cells bounding the lumen. Regulatory mechanisms include systemic, paracrine and autocrine hormones along with their associated intracellular signal pathways. The epithelium lining the semicircular canal duct (SCCD) is a tissue that is known to absorb sodium and calcium and to secrete chloride.
  
  
  RESULTS
  Transport function was assessed by measurements of short circuit current (Isc) and gene transcript expression was evaluated by microarray. Neither ATP nor UTP (100 microM) on the apical side of the epithelium had any effect on Isc. By contrast, basolateral ATP transiently increased Isc and transepithelial resistance dropped significantly after basolateral ATP and UTP. P2Y2 was the sole UTP-sensitive purinergic receptor expressed. Isc was reduced by 42%, 50% and 63% after knockdown of alpha-ENaC, stimulation of PKC and inhibition of PI3-K, while the latter two increased the transepithelial resistance. PKCdelta, PKCgamma and PI3-K were found to be expressed.
  
  
  CONCLUSIONS
  These observations demonstrate that ion transport by the SCCD is regulated by P2Y2 purinergic receptors on the basolateral membrane that may respond to systemic or local agonists, such as ATP and/or UTP. The sodium absorption from endolymph mediated by ENaC in SCCD is regulated by signal pathways that include the kinases PKC and PI3-K. These three newly-identified regulatory components may prove to be valuable drug targets in the control of pathologic vestibular conditions involving dysfunction of transport homeostasis in the ear, such as Meniere's disease.
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506, USA. marcus@ksu.edu.
authors.forename: Satyanarayana R
authors.initials: SR
authors.lastname: Pondugula
authors.forename: Nithya N
authors.initials: NN
authors.lastname: Raveendran
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Marcus
references.citation: Clin Exp Pharmacol Physiol. 2009 Oct;36(10):1016-22
references.pmid: 19566815
references.citation: Am J Physiol Renal Physiol. 2009 Jan;296(1):F10-24
references.pmid: 18508877
references.citation: J Gen Physiol. 2001 Jan;117(1):53-67
references.pmid: 11134231
references.citation: J Gen Physiol. 2002 Dec;120(6):897-906
references.pmid: 12451057
references.citation: J Cell Physiol. 2006 Mar;206(3):759-70
references.pmid: 16245306
references.citation: Am J Physiol. 1999 Jun;276(6):G1391-400
references.pmid: 10362642
references.citation: Am J Physiol Renal Physiol. 2003 Nov;285(5):F833-42
references.pmid: 14532162
references.citation: EMBO J. 2001 Dec 17;20(24):7052-9
references.pmid: 11742982
references.citation: Hear Res. 2008 Jan;235(1-2):1-7
references.pmid: 17980525
references.citation: Am J Physiol. 1999 Sep;277(3):C531-6
references.pmid: 10484339
references.citation: J Biol Chem. 1998 May 29;273(22):13469-74
references.pmid: 9593680
references.citation: Am J Physiol Renal Physiol. 2007 May;292(5):F1314-21
references.pmid: 17200157
references.citation: Am J Physiol Cell Physiol. 2001 Jun;280(6):C1485-97
references.pmid: 11350744
references.citation: Pflugers Arch. 2002 May;444(1-2):220-6
references.pmid: 11976935
references.citation: Am J Physiol Renal Physiol. 2001 Feb;280(2):F303-13
references.pmid: 11208606
references.citation: J Biol Chem. 2002 Jan 4;277(1):5-8
references.pmid: 11696533
references.citation: Curr Opin Nephrol Hypertens. 2008 Sep;17(5):533-40
references.pmid: 18695396
references.citation: Am J Physiol Renal Physiol. 2003 May;284(5):F938-47
references.pmid: 12540365
references.citation: Am J Physiol Cell Physiol. 2002 Dec;283(6):C1752-60
references.pmid: 12388054
references.citation: Am J Physiol Renal Physiol. 2004 Jun;286(6):F1127-35
references.pmid: 14996671
references.citation: J Am Soc Nephrol. 1997 Dec;8(12):1813-22
references.pmid: 9402082
references.citation: Physiol Genomics. 2006 Jan 12;24(2):114-23
references.pmid: 16263802
references.citation: Can J Physiol Pharmacol. 2005 Nov;83(11):977-87
references.pmid: 16391706
references.citation: J Biol Chem. 2005 Dec 9;280(49):40885-91
references.pmid: 16204229
references.citation: Br J Pharmacol. 1998 Jun;124(4):832-8
references.pmid: 9690878
references.citation: Pflugers Arch. 2006 May;452(2):188-98
references.pmid: 16374638