Evidence that activation of protein kinase-C can stimulate 1,25-dihydroxyvitamin D3 secretion by rat proximal tubules.
PTH stimulates mammalian renal proximal tubule cell synthesis and secretion of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by a Ca-dependent process. In the present study regulation of 1,25-(OH)2D3 secretion by PTH, phorbol ester 12-O-tetradecanoylphorbol 13-acetate, the Ca ionophore A23187, and calcitonin was evaluated in perifused rat proximal tubule cells isolated by collagenase digestion and centrifugation through Percoll. Tubules from rats fed a low Ca diet secreted 1,25-(OH)2D3 at a rate 2.5 times that of tubule cells from rats fed a normal Ca diet. Perifusion of tubules with human PTH-(1-34) (10(-7) M) induced an immediate and sustained increase in 1,25-(OH)2D3 secretion. Perifusion with either A23187 or 12-O-tetradecanoylphorbol 13-acetate caused transient increases in hormone secretion, while both agents perifused simultaneously resulted in a sustained increase in 1,25-(OH)2D3 secretion. Perifusion of tubule cells with the protein kinase-C (PKC) inhibitor staurosporine blocked the PTH-induced increase in 1,25-(OH)2D3 secretion. Calcitonin had no effect on 1,25-(OH)2D3 secretion rates. The results of the present studies show that an activator of PKC increases 1,25-(OH)2D3 secretion by mammalian proximal tubule cells and suggest that the phospholipase-C/PKC signalling system may mediate PTH stimulation of 1,25-(OH)2D3 secretion.
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Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637.
Tembe
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Favus
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D000470:Alkaloids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D019379:Teriparatide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D000001:Calcimycin; D002116:Calcitonin; D000242:Cyclic AMP; D011493:Protein Kinase C; D002117:Calcitriol; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate