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

• Published in: Experimental physiology 1988-07, Vol.73 (4), p.573-584
• Main Authors: Dacke, C. G., Shaw, A. J.
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - metabolism; Calcium - blood; Calcium - metabolism; Cattle; Chickens; Fundamental and applied biological sciences. Psychology; Hydrogen Peroxide - pharmacology; Male; Metabolisms and neurohumoral controls; Parathyroid Hormone - chemical synthesis; Parathyroid Hormone - pharmacology; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Teriparatide; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Water and mineral metabolism. Osmoregulation. Acidobasic balance
• ISSN: 0958-0670; 0144-8757; 1469-445X
• DOI: 10.1113/expphysiol.1988.sp003177

We have previously demonstrated that intravenous injection of synthetic bovine parathyroid hormone (1-34) (bPTH(1-34)), but not necessarily bPTH(l-84), into chicks rapidly (3 min) inhibits skeletal uptake of an acute 45 Ca 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 [Nle 8 , Nle 18 , Tyr 34 ]-bPTH(l-34)amide reduced chick bone 45 Ca uptake but failed to raise plasma Ca levels. Cyclic AMP formation in response to this analogue was also slight. Another analogue, [Nle 8 , Nle 18 , Tyr 34 ]-bPTH(3-34)amide, failed to inhibit 45 Ca 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 45 Ca 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 45 Ca uptake by stimulating release and turnover of intracellular calcium stores in bone lining cells, thereby creating a gradient for Ca out of bone.