Intestinal smooth muscle contraction and the effects of cadmium and A23187

Pretreatment of the guinea-pig ileal longitudinal muscle preparation with cadmium (Cd++) in the concentration range 5 to 1000 muM resulted in an inhibition of the phasic and tonic contractions induced by both high potassium and the muscarinic agonist, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide. The K+ contracture was significantly more sensitive to the inhibitory action of Cd++ in the concentration range 5 to 100 muM, but not at concentrations of Cd++ above 100 muM. Low concentrations of Cd++, 0.1 to 0.01 muM, were found to increase by an atropine-sensitive mechanism, the spontaneous activity of approximately 50% of the preparations tested. It was also shown that the ionophore A23187 produced a concentration-dependent contraction in the guinea-pig ileal longitudinal muscle that was dependent upon the presence of extracellular calcium. When 1.8 mM Cd++ was added to a tissue that had been incubated in Ca++-free media for 60 minutes and pretreated with 5 muM A23187 for 15 minutes, a slow contractile response was recorded. Similar, but significantly smaller, contractions were also recorded when 1.8 mM Ca++, Mn++, Sr++, Pb++ and Ba++, but not when Co++, Ni++, Hg++, UO2++, and Tm++ and Th++++ were administered. It was concluded that the contractile action of these cations was dependent on ionic radius, hydration energy, valency and, perhaps, coordination number, and was due to the intracellular entry of the cation where it resulted in the release of bound Ca++ and/or directly activated the smooth muscle troponin system.