Effect of leukotriene C4 on electromechanical activity and Ca2+ uptake in taenia coli.
The actions of leukotriene C4 (LTC4) on electromechanical activity and 45Ca2+ uptake in guinea pig taenia coli were investigated. The contractile action of LTC4 was abolished by the removal of extracellular Ca2+. LTC4 concentrations eliciting a maximal contraction in normal medium produced no response in preparations depolarized with KCl. In single sucrose gap studies, LTC4 increased both the frequency of electrical spiking and tension. These effects were blocked by the dihydropyridine Ca2+-channel antagonist PY 108-068 and by the leukotriene receptor antagonist FPL 55712. In double sucrose gap experiments, LTC4 caused a small depolarization without measurable change in membrane conductivity; increased spontaneous electrical activity was again accompanied by an increase in tension. LTC4 caused a detectable increase in 45Ca2+ uptake only at extracellular Ca2+ concentrations less than 1 mM, and this was again inhibited by PY 108-068 or FPL 55712. It is concluded that the contractile effects of LTC4 in guinea pig taenia coli occur as a consequence of its ability to open voltage-sensitive Ca2+ channels, an effect that may occur independently of membrane depolarization.
Zschauer
A
A
Department of Pharmacology, University of Cambridge, United Kingdom.
Matthews
E K
EK
Richardson
B P
BP
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002132:Calcium Radioisotopes; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D012016:Reference Values; D013189:SRS-A / Q000494:pharmacology*
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D013189:SRS-A; D011189:Potassium Chloride; D002118:Calcium