Effects of LTC4 and BW 755C,a blocker of its synthesis,on contraction in smooth muscle and operation of voltage-dependent calcium channels in nerve cells

The effects were investigated of LTC₄, a synthetic leukotriene, and BW 755C, a blocker of LTC₄ biosynthesis, on the operation of Ca channels at the cell membrane and on contraction of muscle fibers using intracellular dialysis and voltage clamping at the membrane of isolated nerve cells and by recording spontaneous contraction of the uterus in white rats at advanced stages of pregnancy. It was found that 1·10^–7 M LTC₄ stimulates the contraction of the uterus without altering its response to oxytocin application. The same concentration of LTC₄ was found to increase calcium conductance by 60±27%. At the same time, a 25±6 mV shift in peak current-voltage relationship along the voltage axis toward negative values was recorded for calcium current. BW 755C, a blocker of the key enzyme in the lipoxygenase metabolic pathway of arachidonic acid, exerts an action similar to leukotriene on calcium conductance, although brief contraction of the uterus is rapidly replaced by complete inhibition of this activity.Institute of Bioorganic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 24–31, January–February, 1989.