Endogenous expression of type II cGMP-dependent protein kinase mRNA and protein in rat intestine. Implications for cystic fibrosis transmembrane conductance regulator

T Markert, A B Vaandrager, S Gambaryan, D Pöhler, C Häusler, U Walter, H R De Jonge, T Jarchau, S M Lohmann

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Certain pathogenic bacteria produce a family of heat stable enterotoxins (STa) which activate intestinal guanylyl cyclases, increase cGMP, and elicit life-threatening secretory diarrhea. The intracellular effector of cGMP actions has not been clarified. Recently we cloned the cDNA for a rat intestinal type II cGMP dependent protein kinase (cGK II) which is highly enriched in intestinal mucosa. Here we show that cGK II mRNA and protein are restricted to the intestinal segments from the duodenum to the proximal colon, with the highest amounts of cGK II protein in duodenum and jejunum. cGK II mRNA and protein decreased along the villus to crypt axis in the small intestine, whereas substantial amounts of both were found in the crypts of cecum. In intestinal epithelia, cGK II was specifically localized in the apical membrane, a major site of ion transport regulation. In contrast to cGK II, cGK I was localized in smooth muscle cells of the villus lamina propria. Short circuit current (ISC), a measure of Cl- secretion, was increased to a similar extent by STa and by 8-Br-cGMP, a selective activator of cGK, except in distal colon and in monolayers of T84 human colon carcinoma cells in which cGK II was not detected. In human and mouse intestine, the cyclic nucleotide-regulated Cl- conductance can be exclusively accounted for by the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Viewed collectively, the data suggest that cGK II is the mediator of STa and cGMP effects on Cl- transport in intestinal-epithelia.

    Original languageEnglish
    Pages (from-to)822-30
    Number of pages9
    JournalJournal of Clinical Investigation
    Volume96
    Issue number2
    DOIs
    Publication statusPublished - Aug 1995

    Keywords

    • 8-Bromo Cyclic Adenosine Monophosphate
    • Animals
    • Biological Transport
    • Carcinoma
    • Cecum
    • Chlorides
    • Colon
    • Colonic Neoplasms
    • Cyclic GMP
    • Cyclic GMP-Dependent Protein Kinases
    • Cystic Fibrosis Transmembrane Conductance Regulator
    • Enterotoxins
    • Enzyme Induction
    • Esophagus
    • Humans
    • In Situ Hybridization
    • Intestinal Mucosa
    • Intestine, Small
    • Isoenzymes
    • Male
    • Membrane Proteins
    • Microvilli
    • Muscle, Smooth
    • Organ Specificity
    • RNA, Messenger
    • Rats
    • Rats, Sprague-Dawley
    • Stomach
    • Tumor Cells, Cultured

    Fingerprint

    Dive into the research topics of 'Endogenous expression of type II cGMP-dependent protein kinase mRNA and protein in rat intestine. Implications for cystic fibrosis transmembrane conductance regulator'. Together they form a unique fingerprint.

    Cite this