Fa. Santos et Vsn. Rao, Quinine-induced inhibition of gastrointestinal transit in mice: possible involvement of endogenous opioids, EUR J PHARM, 364(2-3), 1999, pp. 193-197
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.