Mechanism of inhibition of smooth muscle of guinea-pig taenia coli by chloramphenicol.
The effects of antibiotic chloramphenicol (CAP) on Ca(2+)-ATPase activity and muscle tension were examined in guinea-pig taenia coli. In general, when CAP was added to the resting tissue no inhibition was observed except when a tonus was present, caused by either ouabain, high K+ or acetylcholine. Ouabain and high K(+)-induced sustained contractions were concentration-dependently inhibited by CAP. The sustained contraction induced by high K+ was more strongly inhibited by CAP than ouabain (IC50 value: high K+ 0.29 mumol/ml; ouabain 0.34 mumol/ml). In Ca(2+)-free solution, inhibition of ouabain-induced sustained contracture by CAP was more pronounced. CAP increased the activity of Ca(2+)-ATPase in taenia coli in all experiments. In presence of cystine, CAP-induced inhibition and increase in Ca(2+)-ATPase activity could not be observed. CAP analogue thiamphenicol (TAP), devoid of p-NO2 group, showed insignificant response on smooth muscle inhibition and Ca(2+)-ATPase activity. These findings suggest that CAP inhibits smooth muscle contractility by decreasing cytosolic Ca2+ ([Ca2+]i) level through a cGMP mediated increase in Ca(2+)-ATPase activity and this action is possibly related with the p-NO2 group present in its molecule like other nitro-compounds.
Pramanik
P
P
Department of Physiology, Presidency College, Calcutta, India.
Datta
S C
SC
Mitra
C
C
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002701:Chloramphenicol / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003553:Cystine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013839:Thiamphenicol / Q000494:pharmacology
D003553:Cystine; D010042:Ouabain; D002701:Chloramphenicol; D000252:Calcium-Transporting ATPases; D013839:Thiamphenicol; D006152:Cyclic GMP; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium