Regulation of parathyroid hormone release in normal and pathological parathyroid cells exposed to modulators of protein kinase C

Acta Endocrinol (Copenh). 1992 Jun;126(6):505-9. doi: 10.1530/acta.0.1260505.

Abstract

Effects of the protein kinase C activating phorbol ester 12-O-tetradecanoyl phorbol 13-acetate and the inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) on parathyroid hormone (PTH) release were studied in normal bovine and pathological human parathyroid cells. An increase of extracellular Ca2+ from 0.5 to 3.0 mmol/l inhibited PTH release by 60% in the bovine cells with half maximal effect (ED50) at 1.31 mmol/l. This inhibition reached less than 50% in the cells from patients with primary and uremic hyperparathyroidism, and the ED50 values were 1.49 and 1.42 mmol/l, respectively. The phorbol ester (0.1 mumol/l) made secretion insensitive to changes of extracellular Ca2+, an action counteracted by H-7 (50 mumol/l) in the bovine cells, whereas H-7 alone had no effects. The phorbol ester and H-7 had opposite actions on regulation of PTH release also from cells from patients with hyperparathyroidism. However, in pathological cells H-7 alone improved Ca2+ inhibition of secretion by stimulating release in low Ca2+ concentrations and decreasing the ED50 values. The magnitude of changes in ED50 values by H-7 increased with the severity of the secretory disturbance of the pathological cells. The results indicate that increased protein kinase C activity may be a factor of importance in the pathophysiology of hyperparathyroidism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Adenoma / physiopathology
  • Animals
  • Calcium / pharmacology
  • Cattle
  • Humans
  • Hypercalcemia / etiology
  • Hypercalcemia / physiopathology
  • Hyperparathyroidism / physiopathology
  • Hyperplasia
  • Isoquinolines / pharmacology
  • Parathyroid Diseases / pathology
  • Parathyroid Diseases / physiopathology*
  • Parathyroid Glands / metabolism*
  • Parathyroid Hormone / metabolism*
  • Parathyroid Neoplasms / physiopathology
  • Piperazines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Uremia / complications

Substances

  • Isoquinolines
  • Parathyroid Hormone
  • Piperazines
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Calcium