Parathyroid hormone uses both adenylate cyclase and protein kinase C to regulate acid production in osteoclasts.
Osteoclasts, isolated from the endosteum of 2.5- to 3-week-old chickens, were treated with acridine orange, a hydrogen ion concentration-sensitive fluorescent dye, in order to monitor changes in acid production. The adenylate cyclase inhibitor, alloxan, blocked parathyroid hormone (PTH)-stimulated acid production. Dibutyryl cyclic adenosine monophosphate, a membrane-permeant form of cyclic adenosine monophosphate, mimicked the PTH effect. Bisindolylmaleimide, a specific inhibitor of protein kinase C (PKC), blocked the initial stimulation (15, 30, and 60 min) of acid production by PTH but had no effect on long-term stimulation (120 min). Confocal microscopy of osteoclasts stained with fluorescein-conjugated bisindolylmateimide revealed a shift in location of PKC from the cytoplasm to the plasma membrane region after treatment with parathyroid hormone. The results of these studies support the hypothesis that PTH regulation of acid production in osteoclasts involves both adenylate cyclase and PKC as effectors.
May
L G
LG
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802, USA.
Gay
C V
CV
D000165:Acridine Orange; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000378:metabolism; D008301:Maleimides / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015290:Second Messenger Systems
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007211:Indoles; D008301:Maleimides; D010281:Parathyroid Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000165:Acridine Orange; D016650:Fluorescein-5-isothiocyanate; C088060:bisindolylmaleimide