Journalartikel

Jahr der Veröffentlichung: 2001

Seiten: 603-613

Zeitschrift: Pflügers Archiv European Journal of Physiology

Bandnummer: 442

Heftnummer: 4

ISSN: 0031-6768

DOI Link: https://doi.org/10.1007/s004240100574

Verlag: Springer

Abstract: 
Ca2+-dependent secretagogues evoke only a transient Cl- secretion in intestinal epithelia, although they induce a prolonged increase in the intracellular Ca2+ concentration, suggesting that they may exert an additional antisecretory action. In order to study the mechanism of this antisecretory effect, Cl- secretion, measured as the increase in short-circuit current (I-sc), was evoked by carbachol in the absence and presence of different inhibitors. Neither a calmodulin antagonist, calmidazolium, nor different inhibitors of the nitric oxide (NO) pathway, i.e. N-omega-nitro-L-arginine (L-NNA) and N-omega-nitro-L-arginine methylester (L-NAME), affected the carbachol-induced I-sc. However, inhibition of phospholipases A(2) (PLA(2)) by quinacrine or arachidonyltrifluoromethyl ketone (AACOCF(3)) enhanced the I-sc response evoked by carbachol, suggesting a role of fatty acids in the downregulation of anion secretion. Neither econazole, a cytochrome P450 inhibitor, nor nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenases, mimicked the action of the PLA(2) blockers. Conversely, short- or medium-chain fatty acids inhibited the carbachol- and forskolin-induced I-sc with caprate (C10:0) being the most efficient water-soluble fatty acid. This fatty acid inhibited a Cl- current, which was driven across the apical membrane by a serosally to mucosally directed Cl- gradient after depolarization of the basolateral membrane. A second action site of fatty acids seems to be the basolateral membrane. After permeabilization of the apical membrane with the ionophore nystatin, a mucosally to serosally directed K+ gradient induced a K+ current, which was also inhibited by caprate. These results indicate that carbachol not only acts as a secretagogue but at the same time initializes downregulation by increasing the intracellular concentration of fatty acids, a mechanism limiting the resulting Cl- secretion.

Harvard-Zitierstil: Schultheiss, G., Ribeiro, R. and Diener, M. (2001) Fatty acids inhibit anion secretion in rat colon: apical and basolateral action sites, Pflügers Archiv European Journal of Physiology, 442(4), pp. 603-613. https://doi.org/10.1007/s004240100574

APA-Zitierstil: Schultheiss, G., Ribeiro, R., & Diener, M. (2001). Fatty acids inhibit anion secretion in rat colon: apical and basolateral action sites. Pflügers Archiv European Journal of Physiology. 442(4), 603-613. https://doi.org/10.1007/s004240100574