The final step in the maternal-fetal transfer of calcium in the placenta involves transport against a concentration gradient across the syncytiotrophoblast basal plasma membrane (BM). Based on animal studies, it has been proposed that parathyroid hormone-related peptide (PTHrP) plays a major role in maintaining the maternal-fetal concentration gradient of calcium. In this study, we tested the hypothesis that a highly conserved mid-region fragment (38-94) of PTHrP directly affects the ATP-dependent calcium transport across BM isolated from full-term human placentas. PTHrP (38-94) stimulated ATP-dependent calcium transport at a concentration within the physiological range (5 pg/ml) and the effect (10-38% increase) was concentration dependent over the range 5 pg/ml to 5 ng/ml (n=8; P<0.05). In contrast, PTH, PTHrP (1-34), PTHrP (67-86) and calcitonin increased BM calcium transport only at concentrations much higher than physiological. The increased calcium uptake was inhibited by the protein kinase C (PKC) inhibitor chelerythrine (n=6; P<0.05). In addition, PTHrP (38-94) increased inositol trisphosphate (IP(3)) production and PKC phosphorylation in human placental BM (n=12; P<0.05). Our data indicate that PTHrP (38-94) stimulates Ca(2+)ATPase in the human syncytiotrophoblast BM vesicles by activating the IP(3)-DAG-PKC pathway. We suggest that PTHrP (38-94) is important in maintaining the calcium concentration gradient across the placental barrier in the human.

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