Endogenous nitric oxide modulates morphine-induced constipation.
Administration of morphine in mice causes inhibition of the gastrointestinal transit of a charcoal meal. Morphine-induced constipation in mice seems to depend predominantly on action(s) on the central nervous system since N-methyl morphine, a quaternary derivative, inhibits intestinal transit only when administered intracerebroventricularly (i.c.v.). L- but not D-arginine, given intraperitoneally, reversed the constipation induced by both morphine and its quaternary analogue. L-arginine was ineffective when given i.c.v. and did not reverse atropine-induced constipation. These results suggest that L-arginine preferentially modulates opioid-induced constipation through a stereospecific and peripheral action(s). It is possible that the effect of L-arginine is achieved by increasing the amount of nitric oxide released by non-adrenergic, non-cholinergic nerves in the gut. Thus, L-arginine may represent a useful agent for the treatment of undesirable constipation associated with the use of narcotic analgesics.
Calignano
A
A
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Moncada
S
S
Di Rosa
M
M
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001285:Atropine / Q000633:toxicity; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy; D005772:Gastrointestinal Transit / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D009020:Morphine; D001285:Atropine; D001120:Arginine