Resnick L M, Churchill M C, Churchill P C, Laragh J H, Orlowski R
Cardiovascular Center, New York Hospital-Cornell University Medical Center, New York 10021.
Am J Hypertens. 1989 Jun;2(6 Pt 1):453-7. doi: 10.1093/ajh/2.6.453.
We investigated the relation of calcitonin as a calcium-active hormone to its more recently described effects on peripheral vascular tone. Basal renal renin secretion in vitro in rat kidney slices was studied in the presence of salmon calcitonin (SCT, 4400 U/mg), amino acid substituted analogues of SCT, 16-alanine SCT (6200 U/mg) and 12,16,19 tri-alanine SCT (350 U/mg), and of rat calcitonin gene-related peptide (rCGRP). All calcitonin species at the same hypocalcemic activity (1 U/mL) modestly but significantly suppressed renin secretion from control levels (9.79 +/- 0.44 to 7.51 +/- 0.53, 7.70 +/- 0.72, and 7.78 +/- 0.90 Goldblatt units/g/h for SCT, 16-ala SCT, and tri-ala SCT, P less than .05 for all calcitonins v control), whereas rCGRP had no effect. Thus, on a molar basis, the renin suppressing effects of the various calcitonin species paralleled their bioassay-defined calcium sequestering activity, 16-ala SCT greater than SCT much greater than tri-ala SCT. Lower concentrations of SCT (10(-2) U/mL and 10(-4) U/mL, approximately 6 X 10(-10) and 6 X 10(-12) mol/L, respectively) had virtually identical effects. Moreover, verapamil (5 X 10(-6) mol/L) blocked the SCT-induced suppression of renin secretion (9.79 +/- 0.44 v 9.36 +/- 1.05 GU/g/h, P = NS). We conclude that the juxtaglomerular apparatus is a calcitonin-responsive system, in which calcitonin and its analogues act to suppress basal renin secretion in vitro. This effect seems to depend on and may be mediated by modulating cellular calcium uptake, and suggests a wider, calcium-related role for calcitonin than had previously been suspected.
我们研究了作为一种钙活性激素的降钙素与其最近所描述的对外周血管张力的作用之间的关系。在鲑鱼降钙素（SCT，4400 U/mg）、SCT的氨基酸取代类似物、16-丙氨酸SCT（6200 U/mg）和12,16,19-三丙氨酸SCT（350 U/mg）以及大鼠降钙素基因相关肽（rCGRP）存在的情况下，对大鼠肾切片体外基础肾素分泌进行了研究。所有具有相同降钙活性（1 U/mL）的降钙素种类均适度但显著地抑制了对照水平的肾素分泌（SCT、16-丙氨酸SCT和三丙氨酸SCT分别从9.79±0.44降至7.51±0.53、7.70±0.72和7.78±0.90 Goldblatt单位/g/h，所有降钙素与对照相比P＜0.05），而rCGRP则无作用。因此，以摩尔为基础，各种降钙素种类的肾素抑制作用与其生物测定定义的钙螯合活性平行，16-丙氨酸SCT＞SCT＞＞三丙氨酸SCT。较低浓度的SCT（10⁻² U/mL和10⁻⁴ U/mL，分别约为6×10⁻¹⁰和6×10⁻¹² mol/L）具有几乎相同的作用。此外，维拉帕米（5×10⁻⁶ mol/L）阻断了SCT诱导的肾素分泌抑制（9.79±0.44对9.36±1.05 GU/g/h，P =无显著性差异）。我们得出结论，肾小球旁器是一个降钙素反应系统，其中降钙素及其类似物在体外可抑制基础肾素分泌。这种作用似乎取决于并可能通过调节细胞对钙的摄取来介导，这表明降钙素在钙相关方面的作用比以前所怀疑的更为广泛。
