Calcitonin stimulates plasminogen activator in porcine renal tubular cells: LLC-PK1.

Abstract

Plasminogen activators are highly selective proteases that activate the proenzyme plasminogen to the general protease, plasmin. A porcine kidney cell line was studied that was originally isolated as a high producer of plasminogen activator, in which activities of cellular adenylate cyclase and cAMP-dependent protein kinase are increased in response to calcitonin. Salmon calcitonin, in the concentration range 0.03-300 nM, increased plasminogen activator production up to .apprx. 1,000-fold and concurrently inhibited cell multiplication; both of these effects were reversible. Human calcitonin was .apprx. 0.01 times as potent as salmon calcitonin, corresponding to potency differences observed in other biological systems. Plasminogen activator production was also stimulated by other agents that raise cellular cAMP levels such as cholera toxin, phosphodiesterase inhibitors [isobutylmethylxanthine] and vasopressin, but not to the same extent as by calcitonins. The rapidity and sensitivity of the plasminogen activator determination and other cellular responses may make it possible in the future to use this cell strain in a convenient bioassay for calcitonins and their analogs.