title: Reversal of CRF- and dopamine-induced stimulation of colonic motility by CCK and igmesine (JO 1784) in the rat.
abstract: 1. The role of dopamine in the genesis of corticotropin releasing factor (CRF)- and emotional stress (ES)-induced stimulation of colonic motility, as well as the mechanism of antagonistic action of cholecystokinin octapeptide (CCK-8s) and igmesine (alpha sigma receptor ligand, formerly JO 1784) on dopamine-induced colonic hypermotility, have been investigated in the rat. 2. ES and i.c.v. injection of CRF (0.5 microgram kg-1) increased the frequency of colonic spike bursts by 63% and 114%, respectively. Prior i.c.v. administration of (+)-SCH 23390 (a D1 receptor antagonist, 10 micrograms kg-1) significantly (P < 0.05) reduced the CRF- and ES-induced increase in colonic spike burst; whereas, sulpiride (a D2 receptor antagonist, 10 micrograms kg-1) blocked the CRF-induced stimulation of colonic spike bursts but had no effect on the colonic response to stress. 3. I.c.v. injection of dopamine (100 micrograms kg-1), increased colonic spike burst frequency by 54%. (+)-SKF 38393 (5 micrograms kg-1), a selective D1 receptor agonist, and quinpirole (5 micrograms kg-1), a selective D2 receptor agonist, increased colonic spike burst frequency by 71% and 70% respectively. CCK-8s (0.1 microgram kg-1) and igmesine (0.1 microgram kg-1) injected i.c.v. completely prevented the stimulatory effects of dopamine, (+)-SKF 38393 and quinpirole. 4. Previous i.c.v. injection of devazepide, a CCKA receptor antagonist, (10 micrograms kg-1) antagonized the inhibitory effects of both CCK-8s and igmesine injected i.c.v. on dopamine-induced colonic hyperkinesia. 5. These results show that CRF stimulates colonic motility through activation of central dopaminergic mechanisms in response to stress; furthermore, CCK-8s inhibits dopamine-induced colonic hyperkinesia through a mechanism involving D1 and D2 receptors. The sigma receptor ligand igmesine, blocks the CRF and ES-induced colonic hyperactivity via an interaction with central CCK mechanisms.
authors.affiliation: Department of Pharmacology, INRA, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Gué
authors.forename: C
authors.initials: C
authors.lastname: Gleïzes-Escala
authors.forename: C
authors.initials: C
authors.lastname: Del Rio-Lacheze
authors.forename: J L
authors.initials: JL
authors.lastname: Junien
authors.forename: L
authors.initials: L
authors.lastname: Buéno
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D002934:Cinnamates / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology*; D003521:Cyclopropanes / Q000494:pharmacology*; D020109:Devazepide; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D001570:Benzodiazepinones; D002934:Cinnamates; D003521:Cyclopropanes; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D013469:Sulpiride; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D020109:Devazepide; D012844:Sincalide; D004298:Dopamine; C065310:igmesine