Stimulation of membrane-associated protein kinase-C activity in spleen lymphocytes by hPTH-(1-31)NH2, its lactam derivative, [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1-31)NH2, and hPTH-(1-30)NH2

Human parathyroid hormone, hPTH (1-34), stimulates adenylyl cyclase and pho sphatidylinositol-bisphosphate-specific phospholipase-C (PIP2-PLC), as indi cated by increased membrane-associated protein kinase C (PKC) activity in R OS 17/2 rat osteosarcoma cells. The C-terminally truncated hPTH(1-31)NH2 st imulates 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))-hPT H-(1-31)NH2, 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 PIP2-PLC/PKCs in this osteosarcoma line. In contras t, hPTH-(1-31)NH2 [Leu(27)]-cyclo(Glu(22)- Lys(26))-hPTH (1-31)NH2 and even hPTH-(1-30)NH2 can stimulate PKC-activity in freshly isolated rat spleen l ymphocytes as strongly as hPTH-(1-34)NH2. The difference in the ability of membrane-associated PKC activity in spleen lymphocytes, but not in ROS cell s, to be stimulated by C-terminally truncated PTH fragments might be due to different receptor densities or to the lymphocyte's atypical PTH/PTHrP rec eptor. CELL SIGNAL 11;3:159-164, 1999 (C) 1999 Elsevier Science Inc.