Alpha OHD3 Research Articles

Evaluation the Effects of Dietary Cholecalciferol Substitution with 1alpha-Hydroxycholecalciferol on Performance and Tibia Parameters in Broiler Chickens

2 Abstract: This experiment in broiler chickens was conducted to test the efficacy of feeding 1alpha-OH D3 as a replacement for cholecalciferol on performance, tibia quality and severity of tibial dyschondroplasia (TD). On the day of hatch 96 as hatched broiler chickens (Ross-308) were weighted and randomly allocated to two treatment groups, each with 4 replicate pens of 12 chicks. The dietary treatments were as follows: basal diet+5 µg/kg of 1alpha-OHD 3, or basal diet+5000 IU/kg vitamin D3. The broiler house was completely enclosed and lighting was provided by incandescent bulbs. No significant differences (p>0.05) were observed on daily feed intake, body weight and feed conversion ratio whereas it tended to improve in broilers fed basal diet supplemented with 5 µg/kg of 1alpha-OHD3 diet (p>0.05). No significant differences (p>0.05) were found between broilers fed basal diet plus 1alpha-OHD3 or the same basal diet plus cholecalciferol for any of tibia variables measured, whereas it tended to increase in broilers fed basal diet supplemented with 5 µg/kg of 1alpha-OHD3 (p>0.05). Treatments failed to induce any effect on TD scores at d 42, though it tended to increase in broilers fed diets containing 5 µg/kg of 1alpha-OHD 3 (p>0.05). In conclusion, the results indicate that supplementing 1alpha-OHD3 as a replacement for cholecalciferol could promote performance and tibia parameter and it increased severity of TD, whereas the results were not statistically significant.

Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity.

A novel synthesis of a radioactive compound of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) (1) and its pharmacokinetics are described. Radioactive 1 alpha OHD3 tritiated at 22 and 23 positions ([22,23-(3)H4]1 alpha OHD3) (5) was prepared via key reactions of the reduction of acetylenic side chain in the ketone (12) with tritium gas in the presence of palladium-charcoal and the subsequent Wittig reaction with the A-ring synthon (16). [22,23-(3)H4]1 alpha OHD3 (5) showed high specific radioactivity (111.5 Ci/mmol) and was used successfully in pharmacokinetics studies with rats. In the pharmacokinetics studies, the plasma concentration level of the active form of vitamin D3, 1 alpha,25-dihydroxy-vitamin D3 [1 alpha,25(OH)2D3], after oral or intravenous administration of [22,23-(3)H4]1 alpha OHD3 (5), showed longer half-life, lower maximum concentration, and lower area under the curve than those after treatment of 1 alpha,25(OH)2D3 tritiated at 26 and 27 positions (4). These results might suggest a beneficial therapeutic utility of 1 alpha OHD3 (1) over the treatment of 1 alpha,25(OH)2D3 (2).

Activity of various hydroxylated vitamin D3 analogs for improving phosphorus utilisation in chicks receiving diets adequate in vitamin D3

1. Young chicks were used to evaluate the efficacy of 2 new vitamin D3 analogs relative to 1alpha-hydroxycholecalciferol (1alpha-OH D3) for their ability to improve the bioavailability of phytate-bound phosphorus (P) when added to P-deficient maize-soyabean meal diets that were superadequate in cholecalciferol. 2. Both 20-epi-19-nor-1,25-(OH)2 D3 and 20-epi-19-nor-1alpha-OH D3 were observed to have phytate-P releasing activity, as measured by bone ash responses. 3. However, the bioactivity of the 2 new analogs differed when compared with 1alpha-OH D3. The 20-epi-19-nor-1alpha-OH D3 analog had a lower (P 0.05) phytate-P releasing activity (45%) than either 1alpha-OH D3 or 20-epi-19-nor-1,25-(OH)2 D3, which did not differ. 4. A dietary concentration of 10 to 15 mug/kg 1alpha-OH D3 was found to optimize phytate-P utilisation in 2-week-old chicks.

Iron bioavailability in soybean meal as affected by supplemental phytase and 1 alpha-hydroxycholecalciferol

An Fe depletion-repletion chick bioassay was conducted to determine whether supplemental microbial phytase or 1 alpha-hydroxycholecalciferol (1 alpha-OH D3) would improve the bioavailability of Fe in soybean meal (SBM). Weight gain, hemoglobin, and hematocrit were markedly improved when increasing levels (0, 10, 20, and 80 mg/kg) of Fe from analytical grade ferrous sulfate (FeSO4.7H2O) were added to the Fe-deficient casein-dextrose basal diet containing 20 mg Fe/kg. Addition of 19 mg Fe/kg from SBM to the basal diet improved (P < 0.05) hemoglobin and hematocrit, but the response was less than that obtained from 10 mg Fe/kg from FeSO4.7H2O. Phytase (1,430 units/kg), 1 alpha-OHD3 (10 micrograms/kg), or the combination, added to the SBM-fortified basal diet did not further improve hematocrit or hemoglobin, indicating that Fe bioavailability of SBM was not increased by either of these feed additives. Based on standard-curve methodology, and using hemoglobin as a criterion, the relative bioavailability of Fe was 38.5% for SBM, 21.0% for SBM+phytase, 23.2% for SBM+1 alpha-OHD3, and 29.2% for SBM+phytase+ 1 alpha-OHD3.

Utilization of phytate and nonphytate phosphorus in chicks as affected by source and amount of vitamin D3.

Commercial and laboratory-strain crossbred chicks responded (P < .01) markedly to 1alpha-hydroxycholecalciferol (1alpha-OH D3) during the 2nd and 3rd wk of life. Bone-ash responses exceeded 50% when this compound was added at 20 microg/kg to phosphorus (P)-deficient corn-soybean meal diets containing surfeit levels (25 microg/kg) of cholecalciferol (D3). Phosphorus excretion was decreased (P < .01) and, thus, retention was increased (P < .01) when 1alpha-OH D3 was supplemented. A P-deficient (.10% P) casein-amino acid purified diet, devoid of D3, was used to determine whether 15 microg/kg of D3 was sufficient to facilitate optimal absorption of the nonphytate P contained in this diet. Bone ash responded to .075% P addition (KH2PO4), and chicks fed diets with .175% nonphytate P exhibited further bone-ash responses to 15 microg/kg of D3 or 10 microg/kg 1alpha-OH D3. Higher levels of either of these D3 compounds did not produce additional responses. This suggested that 15 to 25 microg/kg of D3 in a P-deficient corn-soybean meal diet (.28% phytate P and .14% nonphytate P) is more than adequate to facilitate optimal absorption of the nonphytate P present in the diet. A P-deficient casein-dextrose diet (.13% nonphytate P and 15 microg/kg D3) was fed in the final chick assay, and chicks fed this diet did not show bone ash responses to 1alpha-OH D3 or to microbial-derived phytase (1,470 units/kg). Thus, with P-deficient corn-soybean meal diets containing at least 15 microg D3/kg, 1alpha-OH D3 supplementation markedly increased weight gain and bone ash because it increased the utilization of phytate P.

Novel pharmacological activity of a vitamin (novel pharmacological action of vitamin D)

The endocrine system to maintain calcium homeostasis involves the active vitamin D, as well as parathyloid hormone (PTH). Based on this 'classical' calcium-regulatory function, 1,25-(OH)2D3 and 1 alpha OHD3 was developed as the drug for vitamin D resistant rickets, renal dystrophy, and osteoporosis. Psoriasis is a chronic skin disease which is characterized by hyperproliferation and abnormal differentiation of epidermis. As an anti-psoriatic drug, 1,24R-(OH)2D3 has been on clinical use. The efficacy for psoriasis is explainable by the differentiation-inducing activity of this compound. 1,25-(OH)2D3 was also reported to suppress proliferation and induce differentiation of tumor cells including breast cancer, colon cancer and so forth, suggesting the possible therapy of malignant tumors. In immune system, active vitamin D3 exerts various effects; 1,25-(OH)2D3 suppresses proliferation and cytokine production in T cells and antibody production in B cells. Animal models of autoimmune diseases and skin-graft suggest active vitamin D becomes a novel immuno suppressant. Since 1,25-(OH)2D3 induces the synthesis of nerve growth factor (NGF), it will be a new therapy for the treatment of neuronal degenerative diseases.

Efficacy of supplemental 1 alpha-hydroxycholecalciferol and microbial phytase for young pigs fed phosphorus- or amino acid-deficient corn-soybean meal diets.

Young pigs (5 wk of age and 8 kg) were used to test the efficacy of 1 alpha-hydroxycholecalciferol (1 alpha-OH D3) and microbial phytase for improving the utilization of phytate phosphorus (P) and amino acids present in corn-soybean meal (SBM) diets. Phytase supplementation (1,200 units/kg) to a vitamin D3-adequate, P-deficient corn-SBM diet elicited a marked response (P < .05) in weight gain and ash content of fibula, scapula, and metatarsal bones, but dietary addition of 1 alpha-OH D3 (20 micrograms/kg) was without effect. A P- and vitamin D3-adequate, amino acid-deficient corn-SBM diet (15.5% CP) also was supplemented with 1,200 units/kg of phytase to evaluate the efficacy of phytase in improving amino acid utilization. Pigs gained faster (P < .05) and more efficiently (P < .05) when this diet was supplemented with limiting amino acids, and phytase addition also increased (P < .05) weight gain, regardless of whether the diet was deficient or adequate in amino acids. Feed efficiency was improved (P < .05) by phytase addition to the amino acid-deficient diet but not to the amino acid-adequate diet. Pigs fed the low-CP, amino acid-fortified diet gained as fast and as efficiently as those fed a 19.5% CP (1.19% lysine) positive-control diet.

Elevated superoxide generation in mononuclear phagocytes by treatment with 1 alpha hydroxyvitamin D3

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) treatment on the superoxide production of phagocytic cells in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was studied. A 3-day treatment of CAPD patients with 3 micrograms per day of 1 alpha OHD3 (high-dose treatment) significantly increased NADPH oxidase and killing activities in peritoneal macrophages and peripheral blood monocytes (P < 0.001) as compared with low-dose (0.25 microgram/day of 1 alpha OHD3) treatment or nontreatment. The high oxidase activity observed in macrophages and monocytes after the treatment with 1 alpha OHD3, correlated significantly to the increase in the amount of the cytosolic factor p47 of the NADPH oxidase as detected by western blotting analysis. Superoxide production by the peripheral blood neutrophils of these patients only slightly increased with 1 alpha OHD3 treatment, and the amount of p47 was not affected by 1 alpha OHD3 administration. In order to evaluate the significance of the oxidase cytosolic factor in dictating oxidase activity, a reconstitution of NADPH oxidase was conducted by mixing macrophage cytosols and membranes in a cell-free system. The addition of macrophage cytosol from patients on high-dose treatment to macrophage membranes from patients in all of the categories of treatment resulted in significantly higher (P < 0.001) superoxide production as opposed to the macrophage cytosol from nontreated patients. These results suggest that 1,25(OH)2D3 causes an increase in NADPH oxidase activity in the peritoneal macrophages and monocytes of CAPD patients by inducing synthesis and elevating the amount of the cytosolic factor p47.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimum route of administration of vitamin D in renal failure.

Vitamin D preparations [1-alpha-hydroxycholecalcifol (1-alpha OHD3) or 1,25-dihydroxycholecalciferol (1,25(OH)2D3)] may be administered orally, subcutaneously, intraperitoneally or intravenously. They may be given daily, sometimes in divided doses, or intermittently in large bolus doses, usually three times per week. A further variable is the timing of administration, which may be at night when the gut calcium load is at a minimum. In at least some studies high dose intermittent bolus administration of vitamin D can reduce parathyroid hormone (PTH) secretion by a mechanism separated in time from an increase in ionized calcium (iCa2+). In addition, some but not all studies have shown an improvement in calcium set point and in parathyroid gland sensitivity to calcium. It is also clear from a number of studies that this treatment can succeed where conventional daily administration has failed. Bolus intravenous therapy is most conveniently given after haemodialysis treatment sessions. Bolus oral therapy, perhaps administered prior to sleep, may achieve a similar objective (PTH suppression without hypercalcaemia) in patients on continuous ambulatory peritoneal dialysis (CAPD). It is also becoming apparent that the parathyroid gland may yet again escape following bolus therapy. The success of bolus therapy may lie in several not mutually exclusive mechanisms: high peak concentrations of 1,25(OH)2D3 directly affecting the parathyroid gland, improved compliance, and a small but significant increase in plasma iCa2+. Further long-term controlled trials are needed before bolus therapy can be generally recommended.

The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma

1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxicity is hypercalcaemia. The cellular action of 1,25(OH)2D3 is mediated by binding to an intracellular protein, the vitamin D receptor (VDR). We have evaluated the activity of 1,25(OH)2D3 and its non-calcaemogenic analogue MC903 in the SU-DHL4 and SU-DUL5 B cell lines which carry the 14;18 translocation characteristic of follicular NHL, and also the expression of the VDR in a range of B cell NHLs. Both agents induced differentiation and had an antiproliferative effect on the SU-DHL4 and SU-DUL5 cell lines. However this occurred at a relatively high concentration (10(-7) M) which exceeds the physiological concentration of 1,25(OH)2D3 by approximately 10(3)-10(4)-fold. Expression of the VDR was low in each cell line and in the low grade lymphoma tumour samples. To account for the observed clinical response to 1 alpha OHD3 (alpha-calcidol) in follicular NHL a network is suggested whereby 1,25(OH)2D3 modulates the activity of CD4+T cells which have previously been shown to promote follicle centre cell proliferation. Vitamin D3 analogues may enable serum levels to be achieved which produce a direct action on follicular lymphoma cells without disturbing calcium metabolism.

Increase of renal 25-hydroxyvitamin D3-24-hydroxylase activity and its messenger ribonucleic acid level in 1 alpha-hydroxyvitamin D3-administered rats: possibility of the presence of two forms of 24-hydroxylase.

Messenger ribonucleic acid (mRNA) levels and activities of renal 25-hydroxyvitamin D3-24-hydroxylase (24-OHase) were determined in 3 groups of rats: vitamin D-deficient, normal, and 1 alpha-hydroxyvitamin D3 (1 alpha OHD3)-administered rats. To measure renal 24-OHase mRNA, a DNA probe complementary to the reported sequence of the recently cloned P450 component was employed. The DNA probe hybridized with 24-OHase mRNA. Northern blot analysis indicated that the size of the transcript was approximately 3.4 kb, which was similar in size to that of the previous report. Oral administration of 1 alpha OHD3 (2 micrograms/kg bw/day x 7 days) markedly increased the plasma concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D), renal 24-OHase activity and the renal 24-OHase mRNA level. However, the levels of 24-OHase mRNA were undetectable in vitamin D-deficient and normal rat kidneys, while a significant amount of 24-OHase activity was observed in the normal rat kidney. In vitamin D-deficient rats, renal 25-hydroxyvitamin D3-1 alpha-hydroxylase activity was markedly elevated and 24-OHase activity was completely abolished. When an oligonucleotide probe complementary to coding sequence of heme binding region was used for dot blot analysis, the mRNA was clearly detected in normal rat kidney. Furthermore, activity of the enzyme was attenuated by human parathyroid hormone (1-34) but the mRNA abundance did not change with 2 nmol (every 4 h, 5 times) of hormone treatment in 1 alpha OHD3-dosed thyroparathyroidectomized rats. The present study demonstrates that induction of 24-OHase activity by 1,25(OH)2D3 occurs at least in large part through increase of the gene expression in the kidney. Furthermore, these findings suggest that 2 forms (inducible and constitutive) of 24-OHase exist in rat kidney, and that the previously cloned P450 component is the inducible form of 24-OHase.

Heterogeneity of pseudohypoparathyroidism type I from the aspect of urinary excretion of calcium and serum levels of parathyroid hormone

Urinary excretion of calcium (Ca) was measured in 9 patients with pseudohypoparathyroidism (PHP) type I--3 with Albright's hereditary osteodystrophy (AHO): AHO(+) and 6 without AHO: AHO(-)--and in 13 with idiopathic hypoparathyroidism (IHP), treated with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3) to maintain serum Ca levels at 8.4-9.5 mg/dl. Fasting urinary excretion of Ca in PHP was significantly lower than that in IHP. Moreover, fasting urinary excretion of Ca in PHP AHO(+) was lower than that in PHP AHO(-). This difference was also seen in the urine after oral loading of Ca. Urinary excretion of sodium (Na) was not different between PHP AHO(+) and PHP AHO(-). Serum levels of immunoreactive PTH in PHP AHO(+) were higher than those in PHP AHO(-). The difference in urinary excretion of Ca between PHP AHO(+) and PHP AHO(-) may come from the difference in the circulating levels of PTH.

Effects of parathyroid hormone on urinary excretion of N-acetyl-β-D-glucosaminidase in idiopathic hypoparathyroidism and pseudohypoparathyroidism

N-acetyl-beta-D-glucosaminidase (NAG) is a lysosomal enzyme predominantly located in renal proximal tubules. In idiopathic hypoparathyroidism (IHP), 100 Units of human PTH (1-34) increased urinary excretion of NAG from 0.029 +/- 0.027 to 0.173 +/- 0.035 U/lGF (p less than 0.05) in two patients before treatment and from 0.025 +/- 0.004 to 0.189 +/- 0.092U/lGF (p less than 0.02) in four patients during treatment with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3). In pseudohypoparathyroidism (PHP), PTH did not significantly increase the urinary excretion of NAG in one patient with before treatment (0.048 to 0.025 U/lGF) and four patients during treatment with active vitamin D3 (0.018 +/- 0.008 to 0.036 +/- 0.015 U/lGF). Increase in urinary excretion of NAG after injection of PTH may be a new indicator of renal effect of PTH.

Effects of active vitamin D3 and parathyroid hormone on the serum osteocalcin in idiopathic hypoparathyroidism and pseudohypoparathyroidism.

Serum osteocalcin was measured in patients with idiopathic hypoparathyroidism or pseudohypoparathyroidism, before or during the treatment with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3). Serum osteocalcin and plasma 1,25(OH)2D were decreased in 11 patients with idiopathic hypoparathyroidism before treatment (2.8 +/- 1.27 ng/ml, P less than 0.001 and 14.3 +/- 4.27 pg/ml, P less than 0.001, respectively). In 24 patients with idiopathic hypoparathyroidism during the treatment, serum osteocalcin and plasma 1,25(OH)2D were within the normal range (4.5 +/- 0.74 ng/ml and 25.7 +/- 5.69 pg/ml, respectively). In five patients with pseudohypoparathyroidism before treatment, plasma 1,25(OH)2D was decreased (15.6 +/- 10.6 pg/ml, P less than 0.001) but serum osteocalcin was normal (7.8 +/- 1.66 ng/ml). In nine patients with pseudohypoparathyroidism during the treatment with active vitamin D3, serum osteocalcin and plasma 1,25(OH)2D were normal (6.8 +/- 1.47 ng/ml and 27.2 +/- 6.0 pg/ml, respectively). Serum PTH in pseudohypoparathyroidism was increased before treatment (0.70 +/- 0.34 ng/ml, P less than 0.05) and was normal during the treatment (0.50 +/- 0.13 ng/ml). In idiopathic hypoparathyroidism, the active vitamin D3 increased serum osteocalcin without PTH. In pseudohypoparathyroidism, PTH may increase serum osteocalcin or modulate the effect of active vitamin D3 on serum osteocalcin.

Effects of endogenous and exogenous parathyroid hormone on tubular reabsorption of calcium in pseudohypoparathyroidism.

Resistance to the proximal tubular actions of PTH is a well defined feature in patients with pseudohypoparathyroidism type I (PsH). However, it is less clear whether there also is resistance to the distal tubular effect of PTH on calcium reabsorption in these patients. Thus, we examined the effects of endogenous and exogenous PTH on calcium reabsorption in seven patients with PsH before and during treatment with 1 alpha-hydroxyvitamin D3 (1 alpha OHD3). Eleven patients with idiopathic hypoparathyroidism served as controls. Before treatment, urinary calcium excretion was comparable in the two groups and did not decrease significantly after PTH infusion in either group. During treatment with 1 alpha OHD3, in contrast, steady state urinary calcium excretion in patients with PsH was much lower than that in patients with idiopathic hypoparathyroidism at comparable serum calcium concentrations and did not exceed the upper limit of the normal range when PsH patients were normocalcemic. Infusion of PTH into 1 alpha OHD3-treated PsH patients led to a significant reduction in urinary calcium excretion, even though PTH had no effect on their urinary cAMP or phosphate excretion. These findings suggest that the renal resistance to PTH in patients with PsH is confined to its proximal tubular actions and does not include its distal tubular effect on calcium reabsorption, at least during treatment with active vitamin D metabolites.

The effect of 1 alpha-hydroxyvitamin D3 on cell-mediated immunity in hemodialyzed patients.

The immunoregulatory effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3), a precursor form of active vitamin D3, was examined in hemodialyzed patients. Four weeks of oral administration of 0.5 micrograms/day 1 alpha OHD3 markedly enhanced the lymphoproliferative responses to mitogens without influencing lymphocyte counts or the ratios of lymphocyte subpopulations. In fact, these responses were nearly normal after treatment. These results suggest that deficiency of 1,25-dihydroxyvitamin D3 may play a role in the impairment of cellular immunity in hemodialyzed patients, and that administration of 1 alpha OHD3 may have therapeutic immunological benefit.

The effect of prednisolone on kidney calcification in vitamin D-treated rats.

Glucocorticoids are often used to treat hypercalcemia due to vitamin D overdosage. We measured the effect of 1.5 mg/day of prednisolone on the amount of calcium deposited in the kidney of rats dosed with either 500 ng/d or 2000 ng/day of 1-alpha OHD2 or 1-alpha OHD3. The rats were given a diet containing 0.3% calcium and 0.5% phosphate. A second group of rats received 2000 ng/d of the vitamin D analogs and a diet which contained only 0.02% calcium. After 6 weeks, rats given the vitamin D analogs had two to six times more calcium in the kidney compared with the controls (0.096-0.276 mg vs. 0.240-1.064 mg). When a pharmacological dose of prednisolone was added to treatment, calcium in renal tissue increased to 0.305-3.083 mg. The urinary output of calcium seemed to be increased by prednisolone whereas the serum calcium was lowered. It appears that glucocorticoids given at the same time as vitamin D compounds increases the risk for nephrocalcinosis possibly due to increased amounts of calcium in the urine.

Effects of 1 alpha OHD2 on bone tissue. Studies of 1 alpha OHD2 and 1 alpha OHD3 in normal rats and in rats treated with prednisolone.

Three months old male rats were fed a diet containing 0.3% calcium and 0.5% phosphate. Prednisolone was added to the diet at a dose of 1.5 mg a day and the effect of oral treatment with 0.5 micrograms 1 alpha OHD2 or 0.5 micrograms 1 alpha OHD3 was studied. After 6 weeks rats given prednisolone had a lower bone mass and bone density. The serum phosphate concentration was also lower. Rats given 1 alpha OHD3 had an increased serum calcium concentration even when simultaneously treated with prednisolone. 1 alpha OHD2 did not cause hypercalcaemia. The decrease in bone density caused by prednisolone was prevented by the administration of 1 alpha OHD2. Rats receiving 1 alpha OHD3 together with prednisolone still exhibited a lower bone density. Furthermore, 1 alpha OHD3 decreased bone mass in normal rats and caused a higher mean value of osteoclasts/area whereas 1 alpha OHD2 reduced the number of osteoclasts/area. The study indicates that 1 alpha OHD2 is an effective vitamin D analogue with a lower tendency to cause bone resorption.

Inhibitory effects of active vitamin D preparations on PTH secretion in rats.

To study the effects of various vitamin D preparations on PTH secretion, serum calcium and urinary excretion of cAMP were monitored in conscious perfused rats, and the influences of a bolus iv injection of the preparations on these parameters were examined. Three hours after the administration of 0.25 microgram/kg (0.6 nmol/kg) of 1 alpha, 24(R)-dihydroxycholecalciferol [1 alpha, 24(OH)2D3], the urinary excretion of cAMP decreased to a level compatible with that of parathyroidectomized (PTX) rats (50% of initial value; p less than 0.05) with no change in the concentration of serum calcium (total and ionized). In PTX rats supplemented with bovine PTH (1 U/h), the vitamin D preparation showed no significant effects either on the urinary excretion of cAMP or on serum calcium. These effects were rather specific for active vitamin D preparations, i.e. 1 alpha, 25(OH)2D3 (0.25 micrograms/kg) and 1 alpha OHD3 (1.25-6.25 micrograms/kg). However, 24,25(OH)2D3 (up to 25 micrograms/kg) had no significant effect on these parameters. These results suggest that, in rats, active vitamin D preparations specifically inhibit PTH secretion without causing a significant increase in the serum calcium concentration, reflecting a direct feedback mechanism between active vitamin D metabolite and the parathyroid glands.

Renal function and 1 alpha-hydroxyvitamin D3 in rabbits with normal renal function and renal insufficiency.

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) on the renal clearance of creatinine was investigated in groups of rabbits with stable renal insufficiency and normal controls. Urine was collected in the two groups for two one-week periods during placebo treatment. Then, 1 alpha OHD3, 0.02 micrograms/kg BW/day, was administered orally and urine was collected during the next two weeks. Weekly blood samples were obtained. The treatment had no significant effect on the serum concentrations of calcium and phosphate in either group. Creatinine clearance decreased significantly in both groups during the 1 alpha OHD3 treatment (p less than 0.05), mainly due to a decreased urinary excretion of creatinine. It is suggested that changes in the renal tubular handling of creatinine caused by 1 alpha OHD3 may be the explanation of the observed effect.