Endothelin I Activates the NAADP Signaling Complex on Myometrial Smooth Muscle Cell

A. Tica, V. Tica, O. S. Tica, E. Dun, S. Berceanu, I. Tica

Abstract: There are two main types of intracellular calcium stores: smooth endoplasmic and lysosomal, the last one being activated by nicotinic acid adenine dinucleotid phosphate (NAADP). We decided to study the role of NAADP-sensitive calcium stores on endothelin I (E I)-induced uterine contraction, using bafilomycin B1 (BAF), a lysosomal vesicles destroyer. This is the first study on E I effects on mobilization of lysosomal calcium stores în uterine smooth muscle, secondary to NAADP-dependent pathway activation. We compared the E I 10-8M-induced contractions on non pregnant rat uterine strips, before and after BAF 10-6M administration. BAF decreased the amplitude of E I-induced contractions with 28,43±11% and the frequency with 7,3±3%. No impact on automatic uterine activity was noted. The calcium mobilized from NAADP-sensitive stores has important roles on the amplitude of E I-induced contraction. Its functions on membranal depolarizing (phenomenon responsible for frequency of contractile oscillations) is far less intense, either on induced or on spontaneous contractions.
Keywords: myometrium, calcium stores, lysosomes, NAADP, endothelin I, bafilomycin B1