Effect of sulfidopeptide leukotrienes D4 and E4 on ileal ion transport in vitro in the rat and rabbit.
Effects of leukotrienes D4 and E4 (LTD4 and LTE4) on electrolyte transport were examined, employing stripped segments of rat and rabbit ileum mounted in Ussing chambers. Addition of LTD4 or LTE4 to the serosal but not the mucosal bathing solution elicited a transient increase in short-circuit current (Isc) with maximal responses seen at 10(-5) M and 10(-8) M in rat and rabbit respectively and a sustained decrease in transepithelial conductance (Gt) in the rat only. In the rat, Cl replacement, reduction of bathing solution [Ca2+] to 1 microM or pretreatment with 1 microM indomethacin or meclofenamic acid inhibited the LTD4- or LTE4-induced Isc changes with no effect on the decrease in Gt. LTD4 (10 microM) transiently increased net Cl secretion and produced a sustained decrease in both unidirectional and net Na transport and mucosal-to-serosal Cl flux in rat ileum. The decrease in unidirectional Na fluxes is accounted for predominantly by a change in the potential independent flux of Na. These results suggest that the increase in Isc in both rat and rabbit is mediated by arachidonic acid metabolites, whereas the decrease in Gt and net Na absorption in rat ileum is mediated by a cyclooxygenase-independent pathway.
Smith
P L
PL
Department of Advanced Drug Delivery, Smith Kline & French Laboratories, Philadelphia, PA 19101.
Montzka
D P
DP
McCafferty
G P
GP
Wasserman
M A
MA
Fondacaro
J D
JD
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D017999:Leukotriene E4; D008297:Male; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D013045:Species Specificity
D002712:Chlorides; D013189:SRS-A; D017999:Leukotriene E4; D012964:Sodium; D007213:Indomethacin