We have previously shown that
cisapride, a substituted piperidinyl
benzamide, stimulates contraction of healthy feline colonic smooth muscle. The purpose of the present investigation was to determine the effect of
cisapride on feline idiopathic megacolonic smooth muscle function. Longitudinal smooth muscle strips from ascending and descending colon were obtained from cats with idiopathic
megacolon, suspended in a 1.5 mM Ca(2+)-
HEPES buffer solution (37 degrees C, 100% O2, pH 7.4), attached to isometric force transducers, and stretched to optimal muscle length (Lo). Control responses were obtained at each muscle site with
acetylcholine (10(-8) to 10(-4) M),
substance P (10(-11) to 10(-7) M), or
potassium chloride (10 to 80 mM). Muscles were then stimulated with cumulative (10(-9) to 10(-6) M) doses of
cisapride in the absence or presence of
tetrodotoxin (10(-6) M) and
atropine (10(-6) M), or in a 0
calcium HEPES buffer solution. In cats with idiopathic
megacolon,
cisapride stimulated contractions of longitudinal smooth muscle from both the ascending and the descending colon.
Cisapride-induced contractions were similar in magnitude to those induced by
substance P and
acetylcholine in the ascending colon, but were less than those observed in the descending colon.
Cisapride-induced contractions in megacolonic smooth muscle were only partially inhibited by
tetrodotoxin and
atropine, but were virtually abolished by removal of extracellular
calcium. We concluded that
cisapride-induced contractions of feline megacolonic smooth muscle are largely smooth muscle mediated and dependent on influx of extracellular
calcium.
Cisapride-induced contractions in megacolonic smooth muscle are only partially dependent on enteric
cholinergic nerves. Thus,
cisapride may be useful in the treatment of cats with idiopathic
megacolon.