title: Elevated Ca2+ does not inhibit the 1,25(OH)2D3 response to phosphorus restriction.
abstract: Phosphorus restriction and parathyroid hormone (PTH) are the most potent stimuli for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] biosynthesis. Elevated arterial blood ionized calcium (Ca2+) inhibits the PTH-stimulated pathway for 1,25(OH)2D3 production. To determine whether the increase in Ca2+ due to chronic metabolic acidosis (CMA) would prevent stimulation of 1,25(OH)2D3 by dietary phosphorus restriction, rats were fed either a normal (NPD, 0.65%)- or low (LPD, 0.1%-phosphorus diet for 10 days. Ammonium chloride (NH4Cl) was added (1.5%) to the drinking water of some rats (CMA) while others served as nonacidemic controls. LPD increased serum 1,25(OH)2D3 levels in the absence of CMA and CMA did not affect the increase of 1,25(OH)2D3. LPD decreased serum phosphorus and increased Ca2+. Serum 1,25(OH)2D3 levels were correlated inversely with serum phosphorus and directly with Ca2+. Using stepwise linear regression the correlation between phosphorus and 1,25(OH)2D3 accounted for the majority of the variance contributed by both phosphorus and Ca2+ (F = 12.30, P less than 0.001). Increased Ca2+ induced by CMA does not inhibit the rise in serum 1,25(OH)2D3 during LPD, indicating that during phosphorus restriction Ca2+ does not inhibit production of 1,25(OH)2D3. Thus the mechanism whereby PTH and phosphorus restriction stimulate 1,25(OH)2D3 production differ; increased Ca2+ blocks the PTH-mediated rise in 1,25(OH)2D3 but does not alter the 1,25(OH)2D3 response to phosphorus restriction.
authors.affiliation: Department of Medicine, University of Chicago, Illinois 60637.
authors.forename: D A
authors.initials: DA
authors.lastname: Bushinsky
authors.forename: C
authors.initials: C
authors.lastname: Nalbantian-Brandt
authors.forename: M J
authors.initials: MJ
authors.lastname: Favus
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000097:blood*; D002245:Carbon Dioxide / Q000097:blood; D004032:Diet; D004573:Electrolytes / Q000652:urine; D006863:Hydrogen-Ion Concentration; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010758:Phosphorus / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
chemical_list: D001639:Bicarbonates; D004573:Electrolytes; D000643:Ammonium Chloride; D002245:Carbon Dioxide; D010758:Phosphorus; D002117:Calcitriol; D010100:Oxygen; D002118:Calcium