title: Effects of cisapride on feline colonic smooth muscle function.
abstract: OBJECTIVE
  To determine the effects of cisapride on feline colonic smooth muscle function.
  
  
  METHODS
  In vitro smooth muscle mechanical measurements.
  
  
  METHODS
  Intact colon was obtained from healthy 2- or 3-year-old cats.
  
  
  METHODS
  Longitudinal smooth muscle strips from proximal and distal portions of feline colon were suspended in physiologic buffer solution (37 C. 100% O2, pH 7.4), attached to isometric force transducers, and stretched to optimal muscle length. Control responses were obtained at each muscle site with acetylcholine (10(-8) to 10(-4) M), cholecystokinin (10(-11) to 10(-7) M), substance P (10(-21) to 10(-7) M), or neurotensin (10(-11) to 10(-7) M). Muscles were then stimulated with cumulative (10(-9) to 10(-6) M) or bolus (10(-6) M) doses of cisapride in the absence or presence of tetrodotoxin (10(-5) M) and atropine (10(-6) M), nifedipine (10(-6) M), or calcium-free buffer solution.
  
  
  RESULTS
  Cisapride stimulated contractions of longitudinal smooth muscle from proximal and distal portions of feline colon that were similar in magnitude to contractions induced by substance P and neurotensin. Cisapride contractions were only partially inhibited by tetrodotoxin (10(-6) M) and atropine (10(-6) M), suggesting that cisapride responses are only partially dependent on enteric cholinergic nerves. Nifedipine (10(-6)M) inhibited the maximal contraction to cisapride (10(-6) M) by approximately 80%. Removal of extracellular calcium did not inhibit cisapride contractions to a greater extent than did inhibition by nifedipine, indicating that calcium influx through voltage-dependent calcium channels was predominantly responsible for the dependence of the cisapride contraction on extracellular calcium.
  
  
  CONCLUSIONS
  Cisapride-induced contractions of feline colonic smooth muscle are largely smooth muscle-mediated and dependent on calcium influx, and are only partially dependent on enteric cholinergic nerves.
  
  
  CONCLUSIONS
  Cisapride may be useful in the treatment of feline colonic motility disorders.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 9104-6010, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Washabau
authors.forename: J
authors.initials: J
authors.lastname: Sammarco
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002415:Cats; D002766:Cholecystokinin / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D020117:Cisapride; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D018679:Cholinergic Agonists; D010880:Piperidines; D013373:Substance P; D009496:Neurotensin; D013779:Tetrodotoxin; D001285:Atropine; D002766:Cholecystokinin; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium; D020117:Cisapride