Intracellular signal transduction of parathyroid hormone receptor activation and its pathphysiology

点击翻译按钮获取中文摘要

1. In order to deduce the amino acid sequence of dog parathyroid hormone (PTH) receptors, cDNA cloning was carried out using the cDNA library of the liver and kidney. We found that dog PTH receptors were putative G protein-coupled membrane protein having seven membrane spanning domains and that the amino acid sequence of PTH receptors of the dog was homologus that of human (95.3%), rat (88.0%) or opossum (79.1%). The northern blot analysis showed that PTH receptors were expressed in the kidney, liver, brain, aorta and bone marrow. 2. The effect of PTH on contractions and changes in intracellular Ca^<2+> ( [Ca^<2+>] in) was examined in the rat superior mesenteric artery to know the intracellular signal transduction of the PTH receptor activation. PTH inhibited a contraction and increase in [Ca^<2+>] in induced by phenyrephrine greater than that by high concentrations of KCI (high K). PTH inhibited IP3-induced Ca^<2+> release actibated by phenyrephrine without any effects on Ca^<2+>-induced Ca^<2+> release activated by caffeine. PTH decreased a contraction evoked by high K without inhibitory effects on changes in [Ca^<2+>] in, suggesting that PTH has a direct inhibitory effect on the contractile machinery. Intracellular signal trasduction by the PTH receptor may be coupled with increases in cyclic AMP by the activation of the adenylate cyclase. 3. The characteristics of IP3-induced Ca^<2+> release and the source of Ca^<2+> taken up into Ca^<2+> stores were examined in the intestinal smooth muscle. Ca^<2+> released from the store activated not only the contractile machinery but also Ca^<2+>-activated K^+ channels. Ca^<2+> stores seem to take up into Ca^<2+> preferentially passing through unique Ca^<2+> channels, but not voltage-dependent Ca^<2+> channels. PTH may affect the Ca^<2+> release and/or Ca^<2+> uptake through cyclic AMP-dependent pathways.