Phosphatidic acid modulates Cl- secretion in T84 cells: varying effects depending on mode of stimulation.

Journal Article (Journal Article)

Cl- secretion in T84 cells evoked by a stimulus that activates protein kinase C, carbachol, was associated with elevated levels of 32P-labeled phosphatidic acid (PA). PA's role in the regulation of Cl- secretion was explored by examining the effect of exogenous PA (10(-4) M) on Cl- secretion and intracellular Ca2+ levels ([Ca2+]i) in monolayers. PA potentiated the effect of carbachol on [Ca2+]i and Cl- secretion, although it did not stimulate Cl- secretion by itself. PA had divergent effects on cyclic nucleotide-dependent Cl- secretion. It delayed Cl- secretion induced by vasoactive intestinal polypeptide [VIP, adenosine 3',5'-cyclic monophosphate (cAMP) dependent] but potentiated that induced by the heat-stable enterotoxin of Escherichia coli (STa; guanosine 3',5'-cyclic monophosphate dependent). PA did not alter AMP or GMP levels, suggesting that PA acts at a site distal to the generation of these second messengers. PA caused a slight increase in phosphorylation of protein kinase C substrates but not of cAMP-dependent protein kinase substrates. However, PA is probably not acting through a classical protein kinase C pathway, because we have previously shown that phorbol esters inhibit carbachol's actions, and the protein kinase C inhibitor staurosporine failed to block the effect of PA on VIP- or STa-stimulated Cl- secretion. Thus PA differentially regulates stimulated Cl- secretion in T84 cells, depending on the nature of the agonist.

Full Text

Duke Authors

Cited Authors

  • Vajanaphanich, M; Kachintorn, U; Barrett, KE; Cohn, JA; Dharmsathaphorn, K; Traynor-Kaplan, A

Published Date

  • May 1993

Published In

Volume / Issue

  • 264 / 5 Pt 1

Start / End Page

  • C1210 - C1218

PubMed ID

  • 8388632

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajpcell.1993.264.5.C1210


  • eng

Conference Location

  • United States