Inositol 1,4,5-trisphosphate and oxytocin binding in human myometrium

The presence of inositol 1,4,5-trisphosphate (IP3) receptors in human myometrium has been investigated and their concentration compared with that of oxytocin receptors. Myometrial microsomes were incubated with 3H-IP3 alone and in the presence of unlabeled IP3. Binding was to a single class of noninteracting sites with a density of 1-2 pmol/mg of protein. The sites had characteristics of true IP3 receptors, i.e., very fast association and dissociation rates, high affinity (Kd 25-50 nM) and specificity (IP3 greater than IP3[2,4,5], IP4 much greater than IP5 greater than IP3[1,3,4], IP1, IP2, IP6), and did not metabolize 3H-IP3. The binding was maximal at pH 8, and was inhibited by calcium (IC50 = 80 nM), magnesium (IC50 = 100 microM), heparin (IC50 = 4.5 micrograms/ml), and GTP (IC50 = 150 microM). The concentration and affinity of IP3 receptors were similar in pregnant and nonpregnant myometrium and remained constant during labor. By contrast, the density of oxytocin receptor increased significantly from nonpregnant to pregnant tissue and fell in advanced spontaneous labor but not in advanced induced labor. These results provide new, additional evidence for the involvement of the phosphatidylinositol pathway in the control of uterine contractility.