Involvement of a CCK-dependent capsaicin-sensitive afferent pathway in the inhibitory effect of pinaverium bromide on the colonic motor response to eating in rats.
The effects of pinaverium bromide on the stimulation of colonic motility induced by meal and cholecystokinin (CCK) were investigated in rats chronically fitted with intraparietal electrodes on the proximal colon and previously treated or not by capsaicin. Pinaverium bromide inhibited in a dose-related manner (2-50 mg/kg, per os) the increase in colonic spike burst frequency induced by a 3 g meal or CCK-8 (2 micrograms/kg, i.v.). The CCK-A and CCK-B antagonists, devazepide and L 365260 (100 micrograms/kg, i.p.), respectively, inhibited the postprandial colonic motor response while only L 365260 reduced the CCK-induced stimulation. The effects of pinaverium bromide and CCK antagonists were not observed in capsaicin-treated animals. Moreover, CCK-8 (2 micrograms/kg, i.v.) did not stimulate colonic motility after capsaicin treatment. The inhibition of postprandial colonic motility by pinaverium bromide, given orally at therapeutic doses, involves a CCK-dependent pathway which requires the integrity of capsaicin-sensitive afferents.
Fioramonti
J
J
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Christen
M O
MO
Dupre
I
I
Bueno
L
L
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D003106:Colon / Q000502:physiology*; D003864:Depression, Chemical; D020109:Devazepide; D004435:Eating; D004576:Electromyography; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D010671:Phenylurea Compounds; D019518:Postprandial Period; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D001570:Benzodiazepinones; D002121:Calcium Channel Blockers; D009025:Morpholines; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D020109:Devazepide; D012844:Sincalide; D002211:Capsaicin; C013199:pinaverium