Characterization of CFTR in salivary glands and pancreatic acinar and duct cells

Weizhona Zeng, Min Goo Lee, Julie Diaz, Ron Kopito, Steven Freedman, Calvin Cotton, Philip Thomas, Shmuel Muallem

Research output: Contribution to journalArticlepeer-review

Abstract

CF is generally attributed to defective Cl- transport by the ductal system of secretory glands. We provide here the first immunocytochemical and functional evidence for the expression of CFTR protein and Cl- current in the rat, mouse and rabbit submandibular, parotid and pancreatic acinar cells, a site proximal to the ductal system of these three secretory glands. Antibodies (Ab) recognizing a variety of CFTR epitopes show that duct and acinar cells from all glands and all species express CFTR in the luminal membrane. Specificity of the Ab was verified and an unequivocable demonstration of CFTR in acinar cells was demonstrated by the absence of staining in duct and acinar cells of the submandibular gland of CF-/CF- mice Electrophysiological characterization in single submandibular duct and acinar cells shows the presence of a PKA-activated, voltage- and time-independent, ohmic Cl- current and the absence of repolarization-dependent tail currents, all of which are kinetic properties of the CFTR-dependent Cl- channel. In addition, the channel was activated by the non-hydrolyzable ATP analog AMPPNP and the benzimidazalone, NS004. Channels activated by all activators were inhibited by glibenclamide and a known inhibitory antisera (antiCFTR505-511). The combined immunological, functional and pharmacological evidence allows us to conclude that acinar cells of salivary glands and the pancreas express functional CFTR-dependent Cl- channels Since this site is proximal to the duct, modification of the activity of this channel in acinar cells may be the underiying cause of the abnormal salivary secretion and pancreatic insufficiency typical of CF.

Original languageEnglish (US)
Pages (from-to)A305
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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