Role of protein kinase C on the acute desensitization of renal cortical adenylate cyclase to parathyroid hormone.
The mechanisms of adenylate cyclase desensitization to parathyroid hormone are still unclear. Current evidence suggest that the signal generated after PTH binding to receptors results in activation of adenylate cyclase and stimulation of phospholipase C with subsequent activation of protein kinase C. Recent studies have suggested a role of protein kinase C on the regulation of the PTH-dependent receptor-adenylate cyclase system in cultured cells. Therefore, the present studies were conducted to examine the role of protein kinase C on the desensitization of canine renal cortical adenylate cyclase after an acute exposure in vivo to PTH. A group of normal dogs were treated with a single intravenous injection of 1 microgram/k of syn bPTH (1-34) or Nle bPTH (3-34). Ten minutes later, animals were subjected to bilateral nephrectomy and the kidney cortex processed for preparations of basolateral membranes for determinations of adenylate cyclase activity, as well as membrane and cytosolic fractions for analysis of protein kinase C activity. Animals not treated with PTH were used as controls. PTH administration in vivo resulted in a 46.9 +/- 9.3% decrease in maximal adenylate cyclase activity in vitro in response to syn bPTH (1-34) (P < 0.001). Likewise, PTH binding as measured with 125I-Nle8,18,Tyr34-bPTH (1-34)NH2 showed a 40 +/- 3% decrease. This alterations were associated with a marked translocation of protein kinase C from the cytosol to the membrane. Thus, protein kinase C activity in membrane fractions increased from 160.6 +/- 44.8 pmol Pi/min in controls to 500.4 +/- 123 in PTH treated dogs (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Bellorin-Font
E
E
Centro Nacional de Diálisis y Trasplante, University Hospital of Caracas, Venezuela.
López
C
C
Díaz
K
K
Pernalete
N
N
López
M
M
Starosta
R
R
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007275:Injections, Intravenous; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology
D010281:Parathyroid Hormone; D018016:Receptors, Parathyroid Hormone; D006165:Guanylyl Imidodiphosphate; D012969:Sodium Fluoride; D011493:Protein Kinase C; D000262:Adenylyl Cyclases