Effects of cisapride on feline colonic smooth muscle function.
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.
Washabau
R J
RJ
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 9104-6010, USA.
Sammarco
J
J
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
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