THE EFFECT OF BILE SALTS ON CONTRACTILITY AND CALCIUM DEPLETION OF POLARIZED AND DEPOLARIZED SMOOTH MUSCLE

In 1943, Emmehin showed that bile salts re-versibly inhibited the contractile response of guinea-pig ileum, in vitro, to a variety of stim-ulants. Recently it was found that commercial sodium taurocholate reversibly inhibited acetyl-choline (ACh) contractions of rat uterus, rat ileum and toad stomach muscle even when the muscle was depolarized by isotonic K2SO solu-tion (Laurence and Simmonds, 1963). Moreover, commercial taurocholate reversibly inhibited the contractile response of depolarized, calcium-de-pleted smooth muscle to calcium. There is circumstantial evidence that the re-lease of ionized calcium is involved in the mech-anism linking the events at the cell membrane with the contractile process (Daniel, 1964; Shanes, 1958; Bohr, 1964). Daniel (1964) has suggested that substances producing a general-ized inhibition of contraction produced by a va-riety of stimuli, may act at a step in the final common path to contraction; for example, by preventing the release of calcium from its bound state. The possibility that bile salts might inter-fere with this role of calcium seemed to merit in-vestigation from a pharmacologic point of view, although there is no evidence that the very low concentrations of bile salts present in tissue fluids under physiologic conditions would significantly affect the performance of smooth muscle. The experiments described in this paper were undertaken to see if the effects of bile salts could be ascribed to a surface action or to a deeper effect, and if bile salts affected the mobility of intracellular calcium as indicated by the rate of loss of tissue calcium in calcium-free solu-tions. Results with conjugated and unconjugated pure preparations of bile salts and with com-mercial preparations were compared. Other ster-oids were briefly examined. Received for publication November 30, 1964