Effects of selective oxidation of 1-34 bovine parathyroid hormone on its renal actions in the rabbit.
Oxidation of both of the methionine residues (positions 8 and 18) in parathyroid hormone (PTH) eliminates many of its biological effects. The present studies were performed to examine the actions of 1,34 bovine PTH and 1-34 bovine PTH oxidized selectively at Met 8, at Met 18, and at both sites on renal electrolyte handling and on adenylate cyclase (AC) stimulation. In clearance studies in anesthetized rabbits, PTH caused a phosphaturia and an anticalciuria. PTH also stimulated renal proximal tubular AC in vitro and increased renal cortical cAMP content in vivo. PTH oxidized at Met 18 was anticalciuric, but not phosphaturic, stimulated renal AC and increased cortical cAMP content. PTH oxidized at Met 8 also produced an anticalciuria without a phosphaturia, but only weakly stimulated AC and did not alter cortical cAMP content. PTH oxidized at both Met 8 and Met 18 was phosphaturic but not anticalciuric, was a weak agonist for AC and decreased cortical cAMP content. In the isolated perfused rabbit proximal straight tubule, PTH inhibited fluid and phosphate transport, whereas the doubly oxidized peptide was inactive. The data are consistent with the possibility that the effects of PTH on renal tubular phosphorus transport are mediated by more than one mechanism and are, in part, independent of the cAMP messenger system.
Pitts
T O
TO
Department of Medicine, University of Pittsburgh School of Medicine, Pa.
Puschett
J B
JB
Rose
M E
ME
Zull
J E
JE
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001692:Biological Transport; D001794:Blood Pressure; D002118:Calcium / Q000097:blood / Q000652:urine; D000242:Cyclic AMP / Q000378:metabolism; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D010084:Oxidation-Reduction; D010281:Parathyroid Hormone / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood / Q000652:urine; D011817:Rabbits
D001639:Bicarbonates; D010281:Parathyroid Hormone; D010758:Phosphorus; D007444:Inulin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium