Stimulation of Membrane-Associated Protein Kinase-C Activity in Spleen Lymphocytes by hPTH-(1–31)NH 2, its Lactam Derivative, [Leu 27]-cyclo(Glu 22-Lys 26)-hPTH-(1–31)NH 2, and hPTH-(1–30)NH 2

Abstract

Human parathyroid hormone, hPTH-(1–34), stimulates adenylyl cyclase and phosphatidylinositol- bisphosphate-specific phospholipase-C (PIP 2-PLC), as indicated by increased membrane-associated protein kinase C (PKC) activity in ROS 17/2 rat osteosarcoma cells. The C-terminally truncated hPTH-(1–31)NH 2 stimulates adenylyl cyclase as strongly as hPTH-(1–34) in these cells, but it does not stimulate PKC activity. Even [Leu 27]-cyclo(Glu 22-Lys 26)-hPTH-(1–31)NH 2, a 6-fold stronger adenylyl cyclase stimulator than hPTH-(1–34), cannot stimulate PKC activity in ROS cells. Therefore PTH required its 32–34 region to stimulate PIP 2-PLC/PKCs in this osteosarcoma line. In contrast, hPTH-(1–31)NH 2 [Leu 27]-cyclo(Glu 22-Lys 26)-hPTH-(1–31)NH 2 and even hPTH-(1–30)NH 2 can stimulate PKC activity in freshly isolated rat spleen lymphocytes as strongly as hPTH-(1–34)NH 2. The difference in the ability of membrane-associated PKC activity in spleen lymphocytes, but not in ROS cells, to be stimulated by C-terminally truncated PTH fragments might be due to different receptor densities or to the lymphocyte's atypical PTH/PTHrP receptor.