title: Effects of synthetic bovine parathyroid hormone (1-34) and its analogues on 45Ca uptake and adenylate cyclase activation in bone and plasma calcium levels in the chick.
abstract: We have previously demonstrated that intravenous injection of synthetic bovine parathyroid hormone (1-34) (bPTH(1-34)), but not necessarily bPTH(1-84), into chicks rapidly (3 min) inhibits skeletal uptake of an acute 45Ca label. In the present study hydrogen peroxide oxidation of bPTH(1-34) abolished this response and reduced its ability to activate adenylate cyclase in bone and kidney. Oxidised bPTH(1-34) did, however, exhibit the full hypercalcaemic activity of untreated hormone. In contrast, the analogue [Nle8, Nle18, Tyr34]-bPTH(1-34)amide reduced chick bone 45Ca uptake but failed to raise plasma Ca levels. Cyclic AMP formation in response to this analogue was also slight. Another analogue, [Nle8, Nle18, Tyr34]-bPTH(3-34)amide, failed to inhibit 45Ca uptake or stimulate cyclic AMP formation in chick bone. It was also without hypercalcaemic activity. These data suggest that the hypercalcaemic response to bPTH(1-34) in chicks is not merely a reflection of its inhibitory effect on bone 45Ca uptake. They also question the relevance of cyclic AMP in the former action. A model is proposed by which PTH could rapidly inhibit bone net 45Ca uptake by stimulating release and turnover of intracellular calcium stores in bone lining cells, thereby creating a gradient for Ca out of bone.
authors.affiliation: Department of Physiology, Marischal College, University of Aberdeen.
authors.forename: C G
authors.initials: CG
authors.lastname: Dacke
authors.forename: A J
authors.initials: AJ
authors.lastname: Shaw
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002417:Cattle; D002645:Chickens; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D010281:Parathyroid Hormone / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D019379:Teriparatide
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D006861:Hydrogen Peroxide; D000262:Adenylyl Cyclases; D002118:Calcium