Carbocyclic thromboxane A2 inhibits Cl- absorption in the rat colon.
The effect of carbocyclic thromboxane A2 (CTXA2) on short-circuit current (Isc) was studied in two preparations of the rat colon descendens, one with and one without the submucosal plexus. In both preparations, CTXA2 (10(-7)-5 x 10(-6) mol.l-1) increased Isc concentration-dependently. Its action was not inhibited by the neurotoxin, tetrodotoxin, or by indomethacin, indicating a direct action on the epithelium. The increase in Isc was dependent on the presence of Cl- and HCO3- anions in the medium, but it was not affected by inhibitors of Cl-secretion such as furosemide or a Cl- channel blocker. Measurements of the unidirectional fluxes of Na+ and Cl-revealed that the dominant action of CTXA2 was an inhibition of the mucosa to serosa flux of Cl-. The action of CTXA2 was prevented by pretreatment with the thromboxane receptor blocker, SK&F 88046. It was also inhibited by TMB-8, a substance preventing the release of Ca2+ from intracellular stores, but its effect was not dependent on the presence of extracellular Ca2+. The results indicate that thromboxanes can modulate Cl-transport through the colonic epithelium by a mechanism dependent on intracellular Ca2+.
Diener
M
M
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Federal Republic of Germany.
Rummel
W
W
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D002712:Chlorides; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C024587:thromboxane A2, carbocyclic; D013928:Thromboxane A2; D002118:Calcium