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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The kappa-opioid receptor agonist asimadoline inhibits epithelial transport in mouse trachea and colon.

The potent kappa-opioid receptor agonist n-methyl-N-[(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidin-1-yl)-ethyl]-2,2-diphenyl-acetamide hydrochloride (asimadoline, EMD 61753) was initially developed for the treatment of chronic pain. Because opioids are well known to reduce secretion and to cause constipation, we investigated the effects on epithelial transport in murine trachea and colon. In Ussing chamber experiments, asimadoline (100 microM) decreased short-circuit currents in airways and colon epithelium. The inhibition of I(SC) was not blocked by naloxone (10 microM) or nor-binaltorphimine (10 microM), suggesting that the response was not mediated by kappa-opioid receptors. The effect of asimadoline on I(SC) was concentration-dependent with half-maximal inhibition of I SC at 23.7 (9.5-49.3) microM and was sensitive to the K+ channel blocker charybdotoxin (10 nM). The amiloride-sensitive Na+ current was reduced by asimadoline, but not in cAMP stimulated tissues. Asimadoline strongly inhibited transient Ca2+-dependent Cl- secretion, activated by the muscarinic receptor agonist carbachol (100 microM) or the purinergic agonist ATP (100 microM). Thus, asimadoline inhibits epithelial transport independent of kappa-opioid receptors, by inhibition of basolateral Ca2+-activated and charybdotoxin-sensitive K+ channels.[1]


  1. The kappa-opioid receptor agonist asimadoline inhibits epithelial transport in mouse trachea and colon. Schreiber, R., Bartoszyk, G.D., Kunzelmann, K. Eur. J. Pharmacol. (2004) [Pubmed]
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