Ellison D H, McCarron D A
Am J Physiol. 1984 May;246(5 Pt 2):F551-6. doi: 10.1152/ajprenal.1984.246.5.F551.
We assessed the vascular, phosphaturic, and calcemic responses to several synthetic parathyroid hormone (PTH) analogues. Bovine (b) PTH (1-34), human (h) PTH (1-34), hPTH (53-84), [ Nle8 , Nle18 , Tyr34 ]bPTH (1-34), and [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) were administered in doses between 1 and 500 micrograms/kg as bolus intravenous injections to male Wistar-Kyoto rats aged 18-26 wk. Antagonism of the action of PTH was assessed in rats pretreated with 10 or 100 micrograms/kg [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) followed by 10 micrograms/kg of bPTH (1-34), or with 10 micrograms/kg hPTH (53-84) followed by 10 micrograms/kg hPTH (1-34). Bovine PTH (1-34), hPTH (1-34), and [ Nle8 , Nle18 , Tyr34 ]bPTH (1-34) produced virtually identical log dose-dependent hypotension, with 100 micrograms/kg of each analogue producing a 56% reduction in mean arterial pressure. Neither hPTH (53-84) nor [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) demonstrated any effect on mean arterial pressure at doses up to 500 micrograms/kg. Pretreatment with the inactive analogues failed to antagonize the vasodilating response to either bPTH (1-34) or hPTH (1-34). The vasoactive analogues significantly increased urinary phosphorus excretion while the inactive analogues did not modify it. hPTH (1-34) produced a modest decrease in serum Ca2+ at 1 min after injection. The results document that the vasodilating effect of PTH is a specific action of the peptide. Deletion of the first two amino acid residues abolishes both the phosphaturic and hypotensive effects of the peptide. Acute changes in serum Ca2+ do not appear to be a prerequisite for the vasodilatory response. Inactive analogues of PTH do not antagonize the vascular actions of the peptide.
我们评估了几种合成甲状旁腺激素（PTH）类似物对血管、磷排泄和血钙的反应。将牛（b）PTH（1 - 34）、人（h）PTH（1 - 34）、hPTH（53 - 84）、[Nle8，Nle18，Tyr34]bPTH（1 - 34）和[Nle8，Nle18，Tyr34]bPTH（3 - 34）以1至500微克/千克的剂量作为单次静脉注射给予18 - 26周龄的雄性Wistar - Kyoto大鼠。在用10或100微克/千克的[Nle8，Nle18，Tyr34]bPTH（3 - 34）预处理后再给予10微克/千克的bPTH（1 - 34），或在用10微克/千克的hPTH（53 - 84）预处理后再给予10微克/千克的hPTH（1 - 34）的大鼠中评估PTH作用的拮抗情况。牛PTH（1 - 34）、hPTH（1 - 34）和[Nle8，Nle18，Tyr34]bPTH（1 - 34）产生几乎相同的对数剂量依赖性低血压，每种类似物100微克/千克均使平均动脉压降低56%。hPTH（53 - 84）和[Nle8，Nle18，Tyr34]bPTH（3 - 34）在高达500微克/千克的剂量下对平均动脉压均无任何影响。用无活性类似物预处理未能拮抗对bPTH（1 - 34）或hPTH（1 - 34）的血管舒张反应。有血管活性的类似物显著增加尿磷排泄，而无活性类似物则无此作用。hPTH（1 - 34）在注射后1分钟使血清Ca2+略有下降。结果表明，PTH的血管舒张作用是该肽的一种特异性作用。删除前两个氨基酸残基可消除该肽的磷排泄和降压作用。血清Ca2+的急性变化似乎不是血管舒张反应的先决条件。PTH的无活性类似物不能拮抗该肽的血管作用。
