Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral papaverine has been shown to be capable of antagonizing the constipation induced by a single dose of oral morphine. The primary aim of the present study was to ascertain whether papaverine is also capable of counteracting morphine-induced decrease of upper gastrointestinal transit (UGT) after repeated parenteral administration of the opioid. We next investigated the mechanisms(s) responsible for the counteracting effect of papaverine, by analysing whether this effect was changed by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), dexamethasone, indomethacin or capsaicin. Papaverine, co-administered with morphine, counteracted the morphine-induced decrease in UGT in mice pretreated with morphine for 3 days but did not do so in naive animals. The counteracting effect of papaverine was antagonized by L-NAME, but not by indomethacin. In mice pretreated with both morphine and dexamethasone, papaverine failed to antagonize the effect of morphine. Capsaicin pretreatment completely abolished the effect of a single dose of morphine, the effect being partially restored by the 3 days pretreatment with morphine. In mice pretreated with both capsaicin and morphine, the UGT decrease elicited by morphine was lower than in the other experimental groups and was not modified by papaverine. Our results show that papaverine can counteract the morphine inhibition of UGT in mice repeatedly exposed to the opioid. Papaverine exerts its action through a nitric oxide synthase-mediated mechanism; this mechanism is only effective after repeated morphine administration and does not operate when capsaicin-sensitive afferent neurones are ablated.
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PMID:Counteracting effect of papaverine on morphine inhibition of gastrointestinal transit in mice. 1836 37

Lubiprostone is a chloride (Cl(-)) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K(+)] channel blocker) and apamin (a calcium [Ca(2+)]-dependent K(+) channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K(+) channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K(+) channel through a prostanoid EP receptor-independent mechanism.
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PMID:Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon. 2517 67