Effect of parathyroid hormone on elastase release from human polymorphonuclear leucocytes.
Acute and chronic renal failure are clinical states associated with secondary hyperparathyroidism and increased catabolism. It has been suggested that elevated proteolytic activity is present in the blood in these clinical states. It is, theoretically, possible that the excess blood levels of parathyroid hormone (PTH) in patients with these disorders stimulate release of proteases, since this latter process is calcium dependent and PTH enhances entry of calcium into cells. The present study examined the effect of PTH and its amino- and carboxyterminal fragments on elastase release from polymorphonuclear leucocytes (PMNL), and evaluated the mechanisms underlying such an action. 1-84 PTH stimulated elastase release from PMNL in a dose-dependent and time-dependent manner. This effect of the hormone was abolished by its inactivation as well as by the presence of EDTA. Verapamil, trifluoperazine and W-7 reduced but did not abolish the 1-84 PTH-induced stimulation of elastase release from PMNL. Phorbol ester (PMA) also stimulated elastase release but both PTH or PMA-induced elastase release was blunted by staurosporin, an inhibitor of protein kinase C. The 19-84 carboxyterminal PTH also produced significant stimulation of elastase release from PMNL but the amino-terminal 1-34 PTH or other peptide hormones (insulin, calcitonin, and ACTH) had no stimulatory effect on elastase release.(ABSTRACT TRUNCATED AT 250 WORDS)
Massry
S G
SG
Department of Medicine, University of Southern California, Los Angeles.
Schaefer
R M
RM
Teschner
M
M
Roeder
M
M
Zull
J F
JF
Heidland
A
A
D058186:Acute Kidney Injury / Q000201:enzymology; D000328:Adult; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000201:enzymology; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*
D010281:Parathyroid Hormone; D010196:Pancreatic Elastase