Role of prostanoid EP3/1receptors in mechanisms of emesis and defaecation in ferrets.
Prostanoid EP receptor agonists are used for a number of clinical indications but may be associated with gastric disturbance. In the present studies we used the ferret and sulprostone (30µg/kg, i.p.) to investigate the role of EP3/1receptors in mechanisms of emesis and defaecation. The emetic response was antagonized significantly by (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenlypiperidine hydrochloride (CP-99,994; 10mg/kg, i.p.; P<0.05), but not by metoclopramide (0.3 and 3mg/kg), ondansetron (0.1 and 1mg/kg), or scopolamine (3mg/kg); promethazine (3mg/kg) potentiated emesis by approximately 82% (P<0.05). Out of the drugs tested, only scopolamine (3mg/kg) reduced significantly the defaecatory and/or tenesmus response (P<0.05). Bilateral abdominal vagotomy was ineffective to reduce sulprostone (30µg/kg, i.p.)-induced emesis and defaection and/or tenesmus. However, sulprostone (10µg, i.c.v.) administered into the fourth ventricle was emetic but did not induce defaection or tenesmus. These data suggests that the action of sulprostone to induce emesis and defaecation and/or tenesmus is largely independent of the abdominal vagal system, with emesis involving central mechanisms. Emetic mechanisms appear dissociated from those mediating defaecation and/or tenesmus.
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Kelvin K W
KKW
Kan
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Man K
MK
Wai
Cardiovascular Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G1 0NR, UK.
Robert L
RL
Jones
School of Biomedical Sciences, Faculty of Medicine and Brain and Mind Institute, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. Electronic address: jar@cuhk.edu.hk.
John A
JA
Rudd
D000005:Abdomen / Q000294:innervation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003672:Defecation / Q000187:drug effects; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D005289:Ferrets; D008297:Male; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000819:agonists / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000819:agonists / Q000378:metabolism*; D014628:Vagotomy; D014839:Vomiting / Q000378:metabolism* / Q000503:physiopathology
D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; C016767:sulprostone; D015232:Dinoprostone
Defaecation; Emesis; Ferret; Prostanoid; Sulprostone; Tachykinin