Involvement of neurokinin 1 and 2 receptors in viscerosensitive response to rectal distension in rats.
OBJECTIVE
Tachykinins participate in somatic pain and intestinal motility control. The role of tachykinin receptors in both colonic motor disturbances and visceral pain (abdominal contractions as an index of visceral pain) induced by rectal distension were investigated.


METHODS
Rats were surgically prepared with electrodes implanted on the proximal colon and the abdominal striated muscles. Catheters were implanted in lateral ventricles of the brain. Rectal distension was performed by inflation of a balloon (0.1-1.6 mL) rectally inserted. CP-96,345 and RP-67,580 (neurokinin [NK] 1 antagonists) and SR-48,968 (NK2 antagonist) were injected intraperitoneally (IP) or intracerebroventricularly (ICV) 20 minutes before distension. GR-73,632 and GR-64,639 (NK1, NK2 agonists) were infused intravenously at 0.15 micrograms.kg-1.min-1.


RESULTS
Rectal distension evoked a significant inhibition of colonic motility and an increase in abdominal contractions. CP-96,345 injected ICV (0.2-0.8 mg/kg) or IP (5-10 mg/kg) and RP-67,580 (0.2 mg/kg IP) eliminated distension-induced colonic inhibition but did not affect abdominal response. SR-48,968 did not affect colonic response but significantly reduced visceral pain (0.4, 0.8 mg/kg ICV: 5-10 mg/kg IP). GR-73,632 enhanced the rectal distension-induced colonic inhibition, whereas GR-64,349 induced a greater abdominal response.


CONCLUSIONS
NK1 receptors mediate the rectocolonic inhibitory reflex, whereas NK2 receptors participate in visceral pain; both responses involve central structures.
Julia
V
V
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Morteau
O
O
Buéno
L
L
D000005:Abdomen / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D003106:Colon / Q000502:physiology; D003109:Colonic Diseases, Functional / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000032:analysis / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000032:analysis / Q000502:physiology; D012007:Rectum / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology
D001549:Benzamides; D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018039:Receptors, Tachykinin; D015320:Tachykinins; C068032:GR 73632; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C068031:neurokinin A (3-10), lysyl(3)-glycyl(8)-R-lactam-leucine(9)-; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; C066892:CP 96345