Neuropeptide Y and sigma ligand (JO 1784) suppress stress-induced colonic motor disturbances in rats through sigma and cholecystokinin receptors.
The effects of neuropeptide Y (NPY), sigma ligand (JO 1784) and sulfated cholecystokinin octapeptide (CCK8s) on emotional stress (ES) and corticotropin-releasing hormone (CRH)-induced colonic hypermotility were evaluated in rats equipped with chronically implanted electrodes on the colon and a small catheter into the lateral ventricle of the brain. A 139% (97-172%) increase in colonic spike burst frequency was observed in rats placed in a test cage in which they had previously received electric footshocks, an event assimilated to an ES. Intracerebroventricular injection of CRH (0.5 microgram/kg) mimicked the effects of ES by increasing colonic spike burst frequency by 89.0%. Given i.c.v., both JO 1784 (0.1 microgram/kg) and NPY (0.15 microgram/kg) blocked these stimulatory effects. Similarly, i.c.v. administration of CCK8s (0.1 microgram/kg) abolished both ES and CRH stimulated colonic motility, an effect reproduced by central injection of JMV 180, a cholecystokinin (CCK) derivative with high affinity for CCKA receptors, (1 microgram/kg), but not by JMV 170, a CCK derivative with low affinity for CCKA receptor at similar or higher dose. BMY 14802 (a sigma receptor antagonist) injected s.c. (1 mg/kg) abolished the antagonistic effects of JO 1784 and NPY on the ES-induced colonic hyperkinesia. Injected i.c.v., devazepide (L 364,718), a CCKA receptor antagonist, at 0.1 and 1 microgram/kg, abolished the effect of both JO 1784 and NPY; by contrast L365,260, a CCKB antagonist, required a dose of 10 micrograms/kg to block the antagonistic effect of NPY and JO 1784.(ABSTRACT TRUNCATED AT 250 WORDS)
Gue
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Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Junien
J L
JL
Del Rio
C
C
Bueno
L
L
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology*; D004347:Drug Interactions; D004594:Electrophysiology; D005769:Gastrointestinal Motility / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology*
D002934:Cinnamates; D003521:Cyclopropanes; D009478:Neuropeptide Y; D011949:Receptors, Cholecystokinin; D011957:Receptors, Opioid; D017480:Receptors, sigma; C067232:JMV 170; C058451:JMV 180; D012844:Sincalide; C065310:igmesine