title: Stimulation of membrane-associated protein kinase-C activity in spleen lymphocytes by hPTH-(1-31)NH2, its lactam derivative, [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, and hPTH-(1-30)NH2.
abstract: Human parathyroid hormone, hPTH-(1-34), stimulates adenylyl cyclase and phosphatidylinositol-bisphosphate-specific phospholipase-C (PIP2-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)NH2 stimulates adenylyl cyclase as strongly as hPTH-(1-34) in these cells, but it does not stimulate PKC activity. Even [Leu27]-cyclo(Glu22-Lys26)-hPTH-(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 contrast, hPTH-(1-31)NH2 [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 and even hPTH-(1-30)NH2 can stimulate PKC activity in freshly isolated rat spleen lymphocytes as strongly as hPTH-(1-34)NH2. 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.
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario. jim.whitfield@nrc.ca
authors.forename: J F
authors.initials: JF
authors.lastname: Whitfield
authors.forename: R
authors.initials: R
authors.lastname: Isaacs
authors.forename: S
authors.initials: S
authors.lastname: MacLean
authors.forename: P
authors.initials: P
authors.lastname: Morley
authors.forename: J R
authors.initials: JR
authors.lastname: Barbier
authors.forename: G E
authors.initials: GE
authors.lastname: Willick
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism*
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; C102836:parathyroid hormone (1-31)amide, human; D011493:Protein Kinase C