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

¹ School of Pharmacy and Biomedical Sciences, Portsmouth t9olytechnic, Park Building, King Henry I Street, Portsmouth PO1 2DZ

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 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(l-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.