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.