Peristalsis regulation by tachykinin NK1 receptors in the rabbit isolated distal colon.
In the gastrointestinal tract, tachykinin NK1 receptors are widely distributed in a number of neuronal and nonneuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as noncholinergic excitatory transmitters, the influence of NK1 receptors in the regulation of peristalsis is not known. The selective NK1-receptor antagonists SR-140333 (0.3 and 1 nM) and MEN-10930 (0.3-10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR-140333 was prevented by N(omega)-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, indicating that NK1 receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK1-receptor agonist septide (3-10 nM) significantly inhibited colonic propulsion. In the presence of L-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK1 receptors.
Onori
Luciano
L
Dept. of Internal Medicine and Public Health, Univ. of L'Aquila, Italy. annaggio@katamail.com
Aggio
Annalisa
A
Taddei
Gennaro
G
Loreto
Maria F
MF
Ciccocioppo
Rachele
R
Vicini
Riccardo
R
Tonini
Marcello
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000737:chemistry / Q000502:physiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011812:Quinuclidines / Q000494:pharmacology; D011817:Rabbits; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; C108844:MEN 10930; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C085215:SR 140333; D019335:Nitroarginine; D013373:Substance P; C054725:septide; D001285:Atropine; D019001:Nitric Oxide Synthase; D000409:Alanine; D011761:Pyrrolidonecarboxylic Acid