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.
C A
CA
Maggi
S
S
Manzini
A
A
Meli
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D004386:Duodenum / Q000187:drug effects; D004492:Edetic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014520:Urethane / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds; C013934:octylonium; D014520:Urethane; D002217:Carbachol; D004492:Edetic Acid; D014700:Verapamil; D009543:Nifedipine; D011188:Potassium