Opioid regulation of mucosal ion transport in the mouse isolated jejunum.
Opioid control of mucosal ion transport was examined in intact, full thickness preparations of mouse jejunum in vitro, using standard Ussing chamber techniques. DPDPE and DAMGO were used as selective agonists for delta and mu subtypes of opioid receptors, respectively, whereas U50,488H [trans-(+-)-3,4-dichloro-N-Me-N-[2-(1-pyrrolidinyl]-benzene-acedamid+ ++ e- methanesulfonate] and U69,593 [(5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidiny)-1- oxa-spiro-(4,5)-dec-8-yl]-benzeaneacetamide] were used as selective agonists at the kappa-opioid receptor. When added to the serosal medium of intact tissues, DPDPE, DAMGO, U50,488H and morphine, but not U69,593, produced a concentration-dependent reduction of basal transmural potential difference and short-circuit current (Isc), and an increase in tissue conductance. DPDPE was 41-, 341- and 476-fold more potent than DAMGO, U50,488H and morphine, respectively, in producing these effects, although all these compounds were equiefficacious. DPDPE, but not DAMGO, U50,488H or U69,593, caused a similar effect on basal Isc when added to the mucosal medium. Naloxone produced a rightward shift in the concentration-effect curve for DAMGO and DPDPE, yielding distinct Ke values for naloxone of 9.7 +/- 0.5 and 42.9 +/- 7.9 nM, respectively. In contrast, ICI 174,864, a delta-selective antagonist, blocked the Isc response induced by DPDPE but not DAMGO. The Isc response of U50,488H, however, was neither blocked nor reversed by naloxone or ICI 174,864, nor blocked by norbinaltorphimine, suggesting that the response was not mediated via opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheldon
R J
RJ
Department of Pharmacology, University of Arizona, Health Sciences Center, Tucson.
Rivière
P J
PJ
Malarchik
M E
ME
Moseberg
H I
HI
Burks
T F
TF
Porreca
F
F
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D004573:Electrolytes; D004745:Enkephalins; D011759:Pyrrolidines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D012964:Sodium