Implication of NK1 and NK2 receptors in rat colonic hypersecretion induced by interleukin 1 beta: role of nitric oxide.
OBJECTIVE
Interleukin (IL) 1 beta is known to induce a neurally mediated colonic water secretion in vivo. The aim of this study was to investigate the mechanism of action of IL-1 beta on colonic net water flux and the role of tachykinins and nitric oxide.


METHODS
In anesthetized rats, isolated colonic loops were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent that was collected at 15-minute intervals.


RESULTS
Recombinant human IL-1 beta induced a 30-minute colonic hypersecretion. This effect was blocked by NK1 and NK2 antagonists, tetrodotoxin, and NG-methyl-L-arginine (L-NMA). L-arginine reversed the antisecretory effect of L-NMA on IL-1 beta-induced hypersecretion but did not modify the IL-1 beta-induced hypersecretion. Both NK1 and NK2 agonists induced a colonic hypersecretion, and their effects were blocked by L-NMA and tetrodotoxin. The NK3 agonist had no effect on water movements. The NK2 antagonist abolished the secretory effect of NK1 agonist; in contrast, the NK1 antagonist had no effect on the NK2 agonist-induced secretion.


CONCLUSIONS
IL-1 beta-induced colonic hypersecretion in vivo involves NK1- and NK2-receptor activation in cascade, suggesting a release of substance P and neurokinin A acting through NO release.
Eutamene
H
H
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Theodorou
V
V
Fioramonti
J
J
Bueno
L
L
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001834:Body Water / Q000187:drug effects / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000819:agonists; D011994:Recombinant Proteins / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D007375:Interleukin-1; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D011994:Recombinant Proteins; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001120:Arginine