Effects of hyperoncotic albumin and parathyroid hormone infusion on jejunal electrolyte and water absorption in the rat

Preferential plasma volume expansion by infusion of hyperoncotic albumin solution dialyzed against distilled water (calcium-poor albumin) decreases sodium reabsorption in the dog proximal renal tubule during hydropenia. No such decrease is observed when infusing a calcium-rich hyperoncotic albumin solution. A possible role of parathyroid hormone (PTH) has been postulated. To investigate whether similar changes could be observed in intestinal electrolyte and water absorption, the effects of systemic hyperoncotic albumin infusion on jejunal transport of water, sodium, and calcium were studied in hydropenic rats by perfusing proximal jejunum in situ. It was further sought whether PTH could play a direct role in jejunal electrolyte and water transfer.Following infusion of calcium-poor, sodium-poor hyperoncotic albumin solution (group I), net jejunal absorption of water, sodium, and calcium decreased significantly when compared to control. Concurrently, lumen-to-mucosa (1-m) calcium flux, measured using 45 Ca, diminished significantly. Following infusion of calcium-rich, sodium-poor hyperoncotic albumin solution (group II), no changes in net or unidirectional fluxes were observed. After infusion of calcium-rich, sodium-rich hyperoncotic albumin solution (group III), net jejunal absorption of water and sodium, but not of calcium, were found significantly decreased when compared to control.Plasma ionized calcium increased 10 min after calcium-rich hyperoncotic albumin loading, but decreased significantly at that time when the calcium-poor hyperoncotic albumin solution was infused. However, 30 min after each of the calcium-rich and calcium-poor albumin infusion, plasma ionized calcium was increased in both groups of rats. Plasma immunoreactive PTH was unchanged 30 min after expansion with the calcium-rich solution but it increased significantly after expansion with the calcium-poor solution.Intravenous infusion of bovine PTH (group IV) resulted in a decrease of net jejunal water, sodium, and calcium flux. The decrease in net calcium transport was accompanied by a decrease in 1-m calcium flux. No such changes were observed when PTH was replaced by vehicle (group V).It is concluded that: (1) hyperoncotic albumin infusion induces jejunal water, sodium, and calcium flux changes dependent on the calcium and sodium content of the infused solution: calcium-poor, sodium-poor hyperoncotic albumin infusion leads to a decrease in net jejunal electrolyte and water absorption possibly via stimulation of PTH secretion; (2) sodium-poor hyperoncotic albumin infusion does not modify per se these fluxes in the hydropenic rat; (3) exogenous PTH infusion as well as endogenous stimulation of PTH secretion results in a comparable decrease of jejunal water, sodium, and calcium absorption.     

Effects of saline infusions on calcium concentration in plasma ultrafiltrate and on the ultrastructure of the parathyroid glands of the rat

Summary Experiments have been performed in adult female rats to examine the effects of saline infusion on calcium concentration in plasma ultrafiltrate and on the ultrastructure of the parathyroids as studied with the electron microscope. Intravenous infusions of isotonic saline of at least 10 ml within 30 min decreased calcium concentration in plasma ultrafiltrate from 3.04±0.15 mEq/l to 2.79±0.11 eEq/l (P<0.001). Saline infusions of 2 h duration at a rate of 0.5 ml/min decreased significantly the number of secretory granules in the parathyroid cells and induced considerable growth of the Golgi apparatus. It is concluded, that saline infusions in the rat decrease the ionized fraction of plasma calcium concentration thereby increasing parathormone secretion rate.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.     

Regulation of calcitonin and parathyroid hormone secretion by oestrogens

Calcitonin is a peptide hormone secreted by C-cells which, in humans, are found mainly in the thyroid gland. It now seems that a major physiological function of this hormone in man is the long-term maintenance of the skeleton achieved by control of bone resorption. A marked sex difference in circulating calcitonin levels normally exists, with a relative deficiency in women as compared to men.It has now been found that oestrogens regulate calcitonin secretion and it appears likely that the loss of ovarian function at the menopause accelerates the natural decline in calcitonin secretion which occurs with age. Thus, post-menopausal women are more markedly calcitonin-deficient.Levels of the bone-resorbing hormones, parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D are not elevated post-menopausally and it seems likely that the increased bone resorption which leads to post-menopausal bone loss is due mainly to the loss of oestrogen and calcitonin secretion.     

Effects of antidiuretic hormone on electrolyte reabsorption and secretion in distal tubules of rat kidney

The effects of (1-desamino-8-d-arginine) vasopressin (dDAVP) on water and electrolyte transport in the distal tubule were investigated by micropuncture. Since, in addition to antidiuretic hormone, parathyroid hormone, calcitonin and glucagon stimulate the adenylate-cyclase system in this nephron segment, experiments were performed on hormone-deprived rats, i.e. homozygous DI Brattleboro rats with reduced levels of endogenous parathyroid hormone, calcitonin and glucagon. Along the distal tubule, dDAVP enhanced water, Cl, Na and Ca reabsorption and sharply increased net K secretion. Phosphate transport was left unchanged and Mg reabsorption was not significantly altered by dDAVP between the early and late distal tubule. Antidiuretic hormone also slightly increased water filtration rate in the superficial nephron, which rose in proportion to whole kidney glomerular filtration rate. It is concluded that, in rats: 1) antidiuretic hormone stimulates water, NaCl and Ca absorption and enhances K secretion along the distal tubule and 2) the tubular effects of dDAVP on electrolyte transport in the loop and distal tubule are responsible for decreasing Mg and Ca urinary excretion.     

Effects of calcitonin, parathyroid hormone and its related fragments on acquisition of active avoidance behavior

The acquisition of active avoidance response was studied in rats injected intracerebroventricularly with calcitonin (CT), parathyroid hormone (PTH) or PTH-related fragments. PTH and PTH65-84 facilitated the acquisition of shuttle-box active avoidance behavior as indicated by the number of conditioned avoidance responses and the percentage of animals reaching the learning criterion. PTH1-34 and PTH44-68, on the contrary, inhibited the acquisition of active avoidance behavior, while CT totally suppressed this behavior in the rat. It is possible that the opposite effects of PTH and CT on learning ability of the rat depend on a different action on calcium metabolism.     

Phosphaturic response of hydrocortisone in the presence and the absence of parathyroid hormone

The effect of hydrocortisone (HC) on the renal Pi transport in the presence and in the absence of parathyroid hormone (PTH) in the rat was examined using clearance techniques. During constant infusion of PTH in parathyroidectomized (PTX) rats, HC decreased the reabsorption of Pi from 2.84 to 2.33 mol/min (P<0.001), the Tm_Pi from 4.55 to 3.83 mol/min (P<0.001), the reabs. Pi/GFR values from 0.93 to 0.74 (P<0.001) and the Tm_Pi/GFR from 1.73 to 1.42 mol/ml (P<0.001). In the absence of PTH, HC diminished the Tm_Pi from 8.36 to 6.58 mol/min (P<0.005) and the Tm_Pi/GFR from 3.36 to 2.51 mol/ml (P<0.001). It is concluded that the phosphaturic response of hydrocortisone may be important in the homeostasis of inorganic phosphate in the body.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Fr 239/8)     

Chloride current activated by cyclic AMP and parathyroid hormone in rat osteoblasts

In primary cultures of rat osteoblasts, studied with the whole-cell configuration of the patch-clamp technique, 8-bromo-cyclic AMP (8BrcAMP) forskolin (FS) and 1–34 parathyroid hormone (PTH) were shown to activate a Cl conductance. This conductance shows a pronounced outward rectification, even with symmetrical Cl concentrations. It is blocked partially and reversibly by 4,4-diisothiocyanatostilbene 2,2-disulfonic acid (DIDS) or diphenylcarboxylate (DPC). The blockade induced by DIDS is time-and voltage-dependent. The Cl responses to FS and PTH develop slowly, after a delay of several seconds and are very slowly reversible. These responses were observed only in a fraction of the cells tested and their detection was favoured by cell dialysis. This Cl current should be taken into account for studying possible modulations of the voltage-gated Ca currents of osteoblasts. It is suggested that its physiological role may be related to the well-known morphological changes induced by PTH in osteoblasts. The cyclic AMP-sensitivity, the outward rectification and the sensitivity to dialysis of this Cl current are reminiscent of the properties of the cystic fibrosis-sensitive Cl channels of epithelial cells.     

Evidence for a function of calcium influx in the stimulation of hormone release from the parathyroid gland in the goat

The acute effects of various drugs on the release of parathyroid hormone (PTH) in goats were studied by local infusions in vivo. Infusions of Ca²+ or Sr²+ reduced the PTH secretion rate, whereas hypocalcemia induced by EDTA increased the PTH release. Blockers of voltage sensitive Ca²+ channels (verapamil, D-600 and nifedipine) lowered the PTH secretion rate, while infusion of 4-aminopyridine, which is a blocker of voltage sensitive K+ channels, increased the PTH release. These effects were not due to altered βadrenergic tonus, since the effects persisted when the drugs were administered during contineous infusion of the β-blocker propranolol. We suggest that the parathyroid cells possess voltage sensitive K+ and Ca²+ channels, and that exocytosis of stored PTH depends on the influx of extracellular Ca²+ as in other secretory cells. In order to explain the inverse relationship between the plasma Ca²+ level and the PTH release, we postulate a suppressive effect of the plasma Ca²+ on the membrane permeability to Ca²+ in parathyroid cells.     

Immunocytochemical staining patterns for parathyroid hormone and chromogranin in parathyroid hyperplasia, adenoma, and carcinoma

Parathyroid glands (PGs) contain less secretory granules with presumably less stored parathyroid hormone (PTH) than many other endocrine glands. Immunocytochemical staining for PTH has been hindered by the lack of commercially available, reliable antibodies against human PTH. By treating deparaffinized tissue sections with an antigen-retrieval procedure, immunocytochemical staining for PTH and chromogranin A (CHA) was performed using commercially available monoclonal antibodies to investigate the functional activity of hyperfunctioning PGs, including chief cell hyperplasia (CCH), adenoma, and carcinoma, compared with that of normal PGs. In normal PGs, PTH and CHA immunostaining was diffusely granular in the chief cell cytoplasm, but was weak in oxyphil cells. The immunostaining in hyperfunctioning PGs was less dense in CCH, and adenomas were less intensely stained than the densely stained peripherally located normal rim. The one carcinoma case studied showed less staining at the periphery and in the mid-portion of the tumor. Thus, immunocytochemical staining for PTH and CHA provides further information on stored, immunoreactive PTH status and will improve functional analysis of hyperfunctioning parathyroid glands.     

Distribution and concentration of immunoreactive parathyroid hormone in brain and pituitary of sheep

Summary We have studied the presence of immunoreactive parathyroid hormone (PTH) in the central nervous system and pituitary of sheep. The PTH concentrations were measured radioimmunologically by two different region-specific antibodies. We could demonstrate PTH in various areas of the brain, whole pituitary, parathyroid glands and plasma of 21 sheep. Measurable concentrations of the two different parathyroid regions (35–84 and 44–68 amino acids fragments) were found in all samples.Abbreviations ACTH Adrenocorticotrophic hormone - CT Calcitonin - CSF Cerebrospinal fluid - CPM Counts per min - Leu-ENK Leucine-enkephalin - Met-ENK Methionine-enkephalin - PTH Immunoreactive parathyroid hormone - RIA Radioimmunoassay - TSH Thyroid stimulating hormone - T₄ Thyroxine - T₃ Triiodothyronine     

Effects of parathyroid hormone on renal tubular calcium and phosphate handling

Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the parathyroid gland in response to lowered plasma calcium levels. This hormone acts through the PTH 1 receptor along the nephron to increase urinary phosphate excretion and decrease urinary calcium excretion. In the proximal tubule, PTH inhibits phosphate reabsorption by reducing the abundance of sodium phosphate cotransporters in the apical membrane. PTH likely decreases calcium reabsorption from the proximal tubule, by reducing the reabsorption of sodium, an event necessary for the paracellular movement of calcium across this segment. In the thick ascending limb (TAL), PTH increases calcium permeability and may increase the electrical driving force thereby increasing calcium reabsorption in the TAL. Finally, in the distal convolution, PTH acts to increase transcellular calcium reabsorption by increasing the activity and abundance of the apically expressed calcium channel TRPV5.     

Role of parathyroid hormone in the pathogenesis of the uremic manifestations

Summary A multitude of clinical and experimental data points toward the role of the elevated blood levels of parathyroid in the pathogenesis of the uremic syndrome. The possible pathways through which parathyroid hormone may exert its deleterious effects and evidence for its toxicity are discussed.This work is supported by Contract NO1-AM-7-2218 with the Chronic Uremia Program of the NIAMDD     

甲状旁腺激素1型受体对骨肉瘤细胞炎症因子和血管生成的影响及其机制研究

目的:探讨甲状旁腺激素1型受体（PTHR1）对骨肉瘤细胞炎症因子和血管生成的影响及其机制。方法:培养骨肉瘤MG63细胞,分为PTHR1阴性对照组（si-NC组）和PTHR1小干扰RNA组（si-PTHR1组）,采用实时荧光定量聚合酶链反应（qRT-PCR）检测si-NC组和si-PTHR1组细胞中PTHR1、血管紧张素...     

Effect of parathyroid hormone on renal calcium and magnesium reabsorption in magnesium deficient rats

Tubular magnesium reabsorption was investigated by recollection micropuncture and in vivo microperfusion techniques in acutely thyropara-thyroidectomized rats made magnesium deficient by dietary deprivation. Henle's loop which normally reclaims the major portion of filtered magnesium was examined by elevation of intraluminal magnesium concentration. The transport capacity in these conditions was significantly lower in magnesium deficient rats (41%) compared to normal animals (71%) at comparable magnesium delivery rates. Acute infusion of MgCl₂ further depressed loop magnesium reabsorption independent of intraluminal magnesium delivery. Parathyroid hormone did not alter magnesium transport capacity in magnesium deficient rats but resulted in enhanced transport in acutely hypermagnesemic deficient rats. Calcium reabsorption followed a similar qualitative pattern as magnesium with respect to loop function and urinary excretion. These results are consistent with a depressed transport capacity for magnesium in the loop of Henle of magnesium deficient rats which is independent of intraluminal magnesium delivery and circulating parathyroid hormone level.     

Effect of combination therapy with cimetidine and pirenzepine on plasma parathyroid hormone and calcitonin levels in hemodialyzed patients

Summary In this study we evaluated the effects of an oral combination therapy with cimetidine and pirenzepine on plasma parathyroidhormone (PTH) and calcitonin (CT) levels in 24 patients on maintenance hemodialysis (mean age: 50 years; mean duration of dialysis treatment: 23 months). As compared to the pre-treatment plasma levels of PTH and CT, there were no significant changes of their plasma concentrations during a 4-week administration of 800 mg cimetidine or 100 mg pirenzepine daily, and the concentrations also did not change significantly during the following 4 weeks of combination therapy with cimetidine and pirenzepine in the above mentioned dosage. Serum concentrations of calcium and phosphate and the activity of the alkaline phosphatase showed no significant changes either. Therefore, we suggest that this therapeutic approach cannot be considered for the treatment of uremic hyperparathyroidism.     

Different correlations between plasma protein concentration and proximal fractional reabsorption in the rat during acute and chronic saline infusion

Summary The effect of acute and chronic saline infusion on filtration and reabsorption in the proximal convolution was investigated in micropuncture experiments on rats. In both acute and chronic infusion single nephron filtration rate and total kidney GFR was increased at equal rates.During acute saline infusion there was a reduction of both fractional reabsorption (from 60.5 to 41.9%) and plasma protein concentration (from 5.8 to 5.2 g-%). During chronic infusion of about 70% of BW/day for 9–17 days there was only a slight decrease in proximal fractional reabsorption from 57.1 to 52.2%, whereas plasma protein concentration was much more reduced (from 5.9 to 3.6 g-%).It could be shown that the decrease in plasma protein was accompanied by an even greater reduction of plasma oncotic pressure. We conclude that the variation of peritubular protein concentration and oncotic pressure cannot influence proximal fractional reabsorption under physiological conditions.Supported by the Deutsche Forschungsgemeinschaft.     

人甲状旁腺激素相关蛋白（1-34）对去卵巢大鼠骨密度和骨生物力学性能的影响

目的：观察人甲状旁腺激素相关蛋白氨基端肽(PTHrP 1-34)对去卵巢的骨质疏松大鼠骨密度(BMD)和骨生物力学性能的影响。 方法： 80只4月龄Wistar健康雌性大鼠，其中60只行双侧卵巢摘除术，20只做假手术，6周后各处死10只证实骨质疏松造模成功。剩余50只骨质疏松模型鼠随机分为5个治疗组，每组10只，其它10只假手术组作对照。PTHrP治疗组（PTHrP 20组， PTHrP 40组， PTHrP 80组）分别用20、40、80 μg/kg剂量，每日皮下注射1次PTHrP 1-34；雌二醇治疗组（E2组）用苯甲酸雌二醇40 μg/kg, 每3 d注射1次；安慰剂组及假手术对照组分别用生理盐水，每3 d注射1次。治疗3个月后，测定并比较股骨、腰椎BMD、骨生物力学参数及血清钙、磷、碱性磷酸酶（ALP）水平。结果： 双侧卵巢摘除6周后，大鼠腰椎BMD及腰椎压缩最大载荷明显低于假手术组(P<0.05)。3个月治疗后，PTHrP 40组和PTHrP 80组大鼠股骨、腰椎BMD及骨生物力学性能明显高于安慰剂组，与雌二醇治疗组无显著差异，腰椎BMD明显高于PTHrP 20组（P<0.05）； PTHrP 40组与PTHrP 80组无明显差异。结论： 每日每公斤体重皮下注射40和80 μg PTHrP 1-34对去卵巢骨质疏松大鼠有明显治疗作用。     

The effect of histamine2 and muscarine receptor antagonists on plasma levels of parathyroid hormone and calcitonin

Summary Long-term administration of cimetidine, a histamine₂ receptor antagonist, has been reported to normalize elevated parathyroid hormone (PTH) concentrations in patients with secondary [1] and primary hyperparathyroidism [2] and even to improve the clinical symptoms. We have compared the effect of cimetidine and pirenzepine on PTH and calcitonin (CT) plasma levels in a short-term trial on patients with secondary hyperparathyroidism. After cimetidine a significant effect on PTH was seen within 30 min lasting 30 min and after pirenzepine, within 60 min and lasting 60 min. The effect on CT was only significant after cimetidine.     

Effects of antidiuretic hormone,parathyroid hormone and glucagon on transepithelial voltage and resistance of the cortical and medullary thick ascending limb of Henle's loop of the mouse nephron

The effect of antidiuretic hormone (arginine vasopressin, AVP, 10⁻¹⁰mol.l⁻¹), parathyroid hormone (PTH, 10⁻⁸ mol.l⁻⁸) and glucagon (10⁻⁸ mol.l⁻¹) on the transepithelial potential difference (PD_te) and the transepithelial resistance (R_te) were tested in in vitro perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. When compared with mTAL segments (PD_te: 8.5±0.4 mV,n=16), cTAL segments displayed a high PD_te of 15.7±0.9 mV (n=11) at the beginning of perfusion experiments which reached a value of 9.4±0.6 mV (n =11) after 38±4 min perfusion. Simultaneously R_te increased significantly from 24±3 to 28±1 Ω cm² (n=11). When PTH, AVP or glucagon were added to the bath solution, PD_te increased with PTH from 10.3±0.8 to 15.2±0.8 mV (n=13), with AVP from 10.2±0.5 to 15.0±0.7 mV (n=24) and with glucagon from 11.3±1.9 to 15.3±2.1 mV (n=8). At the same time R_te decreased from 30±3 to 23±2 Ω cm², from 28±1 to 23±1 Ω cm² and from 23±2 to 18±2 Ω cm², respectively. In mTAL segments, AVP and glucagon increased PD_te from 8.4+0.5 to 13.5±0.9 mV (n=11) and from 8.8±0.6 to 12.8±0.6 mV (n=8) respectively, while R_te decreased significantly from 23±1 to 20±1 Ω cm² and from 27±3 to 21±3 Ω cm². PTH, on the other hand, had no effect on PD_te and R_te. Since the response to PTH appeared to be specific to cTAL segments, paired experiments were performed, in which AVP or glucagon were successively tested with PTH on cTAL and mTAL segments, to ascertain the specificity of the hormonal response. In cTAL segments, PTH and AVP increased the equivalent short-circuit current (I_sc=PD_te/R_te) by 82% and 86% respectively, while PTH and glucagon, in another series, increased I_sc by 95% and 81% respectively. In mTAL segments, I_sc was increased in the presence of AVP and glucagon by 88%, and 93% respectively, whereas PTH had no effect. These results indicate that Nacl reabsorption in cTAL segments is stimulated by AVP, PTH and glucagon and in mTAL segments by AVP and glucagon. The amplitude of the response to the hormones is similar in the two segments. The residual stimulation in cTAL segments, however, persists longer than in mTAL segments.