Role for NK(1) and NK(2) receptors in the motor activity in mouse colon.
The present study examined the effects induced by endogenous and exogenous activation of NK(1) and NK(2) receptors on the mechanical activity of mouse proximal colon. Experiments were performed in vitro recording the changes in intraluminal pressure from isolated colonic segments. Electrical field stimulation in the presence of atropine and guanethidine produced a small relaxation, followed by nonadrenergic noncholinergic (NANC) contraction. SR140333, NK(1) receptor antagonist, or SR48968, NK(2) receptor antagonist, significantly reduced the contraction, although SR48968 appeared more efficacious. The co-administration of SR140333 and SR48968 virtually abolished the NANC contraction. [Sar(9), Met(O(2))(11)]-substance P, selective NK(1) receptor agonist, induced a concentration-dependent biphasic effect, contraction followed by reduction of the mechanical spontaneous activity. Both effects were antagonized by SR140333, but not by SR48968. [beta-Ala(8)]-neurokinin A (4-10), selective NK(2) receptor agonist, evoked concentration-dependent contraction, which was antagonized by SR48968, but not by SR140333. The contraction induced by [Sar(9), Met(O(2))(11)]-substance P, but not by [beta-Ala(8)]-neurokinin A (4-10), was reduced by tetrodotoxin or atropine, and increased by N(omega)-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide synthase. The inhibitory effects induced by [Sar(9), Met(O(2))(11)]-substance P were abolished by tetrodotoxin or L-NAME. The results of the present study suggest that in mouse colon both NK(1) and NK(2) receptors are junctionally activated by endogenous tachykinins to cause an additive response. NK(1) receptors appear to be located on cholinergic and on nitrergic neurons as well as on smooth muscle cells, whereas NK(2) receptors seem to be present exclusively on smooth muscle cells.
Mulè
Flavia
F
Dipartimento di Biologia cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. fmule@unipa.it
Amato
Antonella
A
Serio
Rosa
R
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D018727:Muscarinic Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D026941:Sodium Channel Blockers; C062618:substance P, Sar(9)-Met(O2)(11)-; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine; D015288:Neurokinin A