Regional selectivity of calcium blockers at intestinal level.

Exposure of isolated segments of rat duodenum and proximal colon to either high K+ (55.9 mM) or carbachol (0.1 mM) produced a typical biphasic contraction whose tonic component appears to be almost entirely dependent upon the presence of extracellular Ca++. Verapamil and nifedipine suppressed high K+-and carbachol-induced tonic contractions of both duodenum and proximal colon but a large component of carbachol-induced contraction of proximal colon was insensitive to these substances. Verapamil and nifedipine were: a. 5 and 3 times more effective in antagonizing high K+-induced tonic contractions in the rat duodenum than in the proximal colon, respectively, and b. 10 and 4 times more effective in antagonizing high K+ than carbachol induced tonic contractions of rat duodenum, respectively. The verapamil- or nifedipine- resistant component of carbachol induced tonic contraction of proximal colon was suppressed by drugs which, like octylonium bromide and urethane, have been shown to interfere with mobilization of Ca++ from intracellular storage sites. Experiments in Ca++-free medium indicate the existence in the proximal colon of a significant intracellular Ca++ store which could be mobilized during carbachol but not high K+-induced tonic contractions. These findings indicate that, in the rat intestine, significant regional differences exists in Ca++ pools mobilized by different activating stimuli and in sensitivity to the blocking action of drugs which interfere with Ca++ mobilization from either intra- or extracellular Ca++ pools.