Effect of endothelin 1 on ion transport in isolated rat colon.
BACKGROUND
Endothelin may play a significant role in the regulation of gastrointestinal function because it has a variety of biological activities and because endothelin-like immunoreactivity as well as its specific binding sites have been found in the gastrointestinal tract. This study investigated the secretory effect and mechanism of action of endothelin 1 in mammalian large intestine.


METHODS
Distal colonic segments from Sprague-Dawley rats were stripped of their muscle layers and mounted in Ussing chambers. The effects of endothelin 1 on short-circuit current in rat colonic mucosa were studied in the absence or presence of specific inhibitors. Transmural unidirectional 22Na+ and 36Cl- fluxes and endothelin 1-induced prostacyclin release were also measured.


RESULTS
Serosal addition of endothelin 1 evoked a sustained increase in short-circuit current that was significantly reduced by tetrodotoxin or atropine, and virtually abolished by a selective endothelin A receptor antagonist (BQ-123), furosemide, piroxicam, d,I-verapamil, or removal of serosal calcium. Hexamethonium, amiloride, diphenhydramine, or a specific platelet-activating factor antagonist (CV-6209) did not influence the response to endothelin 1. Endothelin 1 significantly decreased net sodium and net chloride absorption and induced a marked increase in prostacyclin release from the serosal surface of stripped colonic mucosa.


CONCLUSIONS
Endothelin 1 has a secretory effect in rat colon. Its action seems to be mediated by cyclo-oxygenase products and enteric nerves via the activation of an endothelin A receptor.
Kiyohara
T
T
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Okuno
M
M
Nakanishi
T
T
Shinomura
Y
Y
Matsuzawa
Y
Y
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000502:physiology; D015777:Eicosanoids / Q000502:physiology; D004594:Electrophysiology; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007422:Intestines / Q000166:cytology / Q000294:innervation; D007477:Ions; D008297:Male; D008407:Mast Cells / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D010456:Peptides, Cyclic / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D015777:Eicosanoids; D016232:Endothelins; D007477:Ions; D010456:Peptides, Cyclic; D010972:Platelet Activating Factor; D012964:Sodium; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium