Quinine-induced inhibition of gastrointestinal transit in mice: possible involvement of endogenous opioids

The effect of quinine, a cinchona alkaloid, was studied on gastrointestinal transit in mice. Intraperitoneal (i.p.) administration of quinine inhibite d the intestinal propulsion of a charcoal suspension at a dose of 100 mg/kg , comparing favorably with 5 mg/kg morphine. In an attempt to probe into th e mechanism underlying this inhibition, a possible modulation by minoxidil (1 mg/kg, p.o.) and glibenclamide (1 mg/kg, p.o.), the drugs that, respecti vely, open and close ATP-sensitive K+ channels was tested on gastrointestin al transit in animals treated or not with quinine or morphine. While minoxi dil produced no significant change of normal transit, glibenclamide signifi cantly increased it. However, both drugs blacked the quinine-induced reduct ion in gastrointestinal transit. In contrast, the inhibitory effect of morp hine on gastrointestinal transit was not modified by either drug. The effec ts of quinine as well as of morphine on gastrointestinal transit were signi ficantly antagonized by naloxone (2 mg/kg, s.c.), a mu-opioid receptor anta gonist but not by yohimbine (1 mg/kg, i.p.), an alpha(2)-adrenoceptor antag onist. Furthermore, quinine at a lower dose (25 mg/kg) that showed no per s e effect on gastrointestinal transit, significantly potentiated the respons e to 2.5 mg/kg morphine. Although the role of ATP-sensitive K+ channels in the action of quinine and morphine was not clarified by the present results , a possible involvement of endogenous opioid(s) in the quinine-induced inh ibition of gastrointestinal transit can be suggested. (C) 1999 Elsevier Sci ence B.V. All rights reserved.