scholarly journals Stimulatory effect of prostaglandin E2 on 1α,25-dihydroxyvitamin D3 synthesis in rats

1983 ◽  
Vol 216 (1) ◽  
pp. 237-240 ◽  
Author(s):  
M Yamada ◽  
T Matsumoto ◽  
N Takahashi ◽  
T Suda ◽  
E Ogata
Keyword(s):  
Vitamin D ◽  
Cyclic Amp ◽  
Prostaglandin E2 ◽  
Vitamin D3 ◽  
Arterial Infusion ◽  
Dihydroxyvitamin D3 ◽  
Significant Stimulation ◽  
Urinary Cyclic Amp ◽  
Stimulation Of

The effect of prostaglandin E2 on accumulation in plasma of 1 alpha,25-dihydroxy[3H]vitamin D3 from 25-hydroxy[3H]vitamin D3 was studied in vivo using vitamin D-deficient thyroparathyroidectomized rats. Intra-arterial infusion of 10-50 micrograms of prostaglandin E2/h caused a significant stimulation of 1 alpha,25-dihydroxy[3H]vitamin D3 production. No significant changes in plasma Ca2+ and Pi concentrations or urinary cyclic AMP excretion were observed after prostaglandin E2 infusion. Theophylline did not enhance the effect of a submaximal dose of prostaglandin E2 on 1 alpha,25-dihydroxy[3H]vitamin D3 production. These data indicate that prostaglandin E2 stimulates plasma accumulation of 1 alpha,25-dihydroxy[3H]vitamin D3 independent of the adenylate cyclase/cyclic AMP system, and suggest that prostaglandin E2 has a modulatory role in the regulation of 25-hydroxyvitamin D3 1 alpha-hydroxylase in the kidney.

Dissociation between plasma, urine, and renal papillary cyclic AMP content following vasopressin and DDAVP

1979 ◽  
Vol 237 (3) ◽  
pp. F218-F225 ◽  
Author(s):  
M. J. Bia ◽  
S. Dewitt ◽  
J. N. Forrest
Keyword(s):  
Cyclic Amp ◽  
Urine Osmolality ◽  
Brattleboro Rats ◽  
Renal Papilla ◽  
Brattleboro Rat ◽  
Clearance Studies ◽  
Urinary Cyclic Amp ◽  
Stimulation Of

The effects of in vivo physiologic doses of vasopressin and 1-deamino-8-D-arginine vasopressin (DDAVP) on the cyclic AMP content of plasma, urine, and renal papillary tissue were determined in the ADH-deficient Brattleboro rat. During clearance studies, plasma cyclic AMP concentrations and both total and nephrogenous urinary cyclic AMP excretion in vasopressin- and DDAVP-treated rats were similar to the values in time-matched controls. In contrast, in situ renal papillary cyclic AMP content was higher (P less than 0.001) in both vasopressin- (35.7 +/- 3.6 pmol/mg protein) and DDAVP- (29.7 +/- 2.2 pmol/mg protein) treated rats compared to controls (15.1 +/- 1.3 pmol/mg protein). Endogenous stimulation of vasopressin by dehydration in normal rats increased both papillary cyclic AMP content (27.1 +/- 2.7 pmol/mg protein) and urine osmolality, whereas no change in papillary cyclic AMP was observed following dehydration in Brattleboro rats (13.6 +/- 0.8 pmol/mg protein) despite an increase in urine osmolality. The results demonstrate that changes in cyclic AMP following in vivo vasopressin are best demonstrated by measurement of in situ cyclic AMP content of the renal papilla, whereas total urinary cyclic AMP and nephrogenous cyclic AMP are not useful indices of tubular sensitivity to this hormone.

Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3

1983 ◽  
Vol 245 (4) ◽  
pp. E359-E364 ◽  
Author(s):  
G. S. Reddy ◽  
G. Jones ◽  
S. W. Kooh ◽  
D. Fraser ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
The Other ◽  
Hydroxyl Group ◽  
Vitamin D Metabolites ◽  
Structural Requirements ◽  
Dihydroxyvitamin D3 ◽  
Hydroxylated Metabolites ◽  
Perfusion Period ◽  
Stimulation Of

Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.

Intestinal metabolism and portal venous transport of 1,25(OH)2D3, 25(OH)D3, and vitamin D3 in the rat

1985 ◽  
Vol 248 (6) ◽  
pp. G633-G638 ◽  
Author(s):  
G. B. McDonald ◽  
K. H. Lau ◽  
A. L. Schy ◽  
J. E. Wergedal ◽  
D. J. Baylink
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
High Performance ◽  
Average Rate ◽  
Venous Blood ◽  
Intestinal Metabolism ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Polar Metabolites

We compared the intestinal absorption of three vitamin D3 sterols and tested the hypothesis that the intestine hydroxylates absorbed vitamin D and transports polar metabolites in portal venous blood. Micellar solutions containing 50 nmol of a radiolabeled vitamin D3 sterol (1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3, or vitamin D3) were placed in closed jejunal segments of rats prepared with lymphatic and mesenteric venous fistulas. Venous blood loss was replaced by infusion of donor rat blood into the saphenous vein. After 1-2 h the rats were killed, and intestinal homogenates, mesenteric blood, and lymph were analyzed. The average rate of absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was two- and fivefold higher than that of 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D3 (D3), respectively. Transport of hydroxylated vitamin D sterols was primarily via the venous route; the average rate of venous transport of 1,25(OH)2D3 was 18.3 X 10(2) nmol X min-1 X g-1 compared with 8.8 X 10(2) for 25(OH)D3 and 0.13 X 10(2) for D3. High-performance liquid chromatography of intestinal and plasma extracts revealed that there was 25-hydroxylation of absorbed D3, 24- and putative 1-hydroxylation of absorbed 25(OH)D3, and prompt portal venous transport of all hydroxylated metabolites. When 1,25(OH)2D3 was infused into the lumen, the composition of radiolabeled sterols found in intestinal homogenates and mesenteric venous plasma was virtually identical to that of the infusate. These studies provide in vivo evidence for the intestinal metabolism of pharmacological quantities of absorbed vitamin D3 sterols and the prompt portal venous transport of more polar metabolites.

Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease

1985 ◽  
Vol 69 (5) ◽  
pp. 561-570 ◽  
Author(s):  
E. Barbara Mawer ◽  
H. J. Klass ◽  
T. W. Warnes ◽  
Jacqueline L. Berry
Keyword(s):  
Vitamin D ◽  
Liver Disease ◽  
Primary Biliary Cirrhosis ◽  
Alcoholic Liver Disease ◽  
Vitamin D3 ◽  
Control Group ◽  
Biliary Cirrhosis ◽  
Vitamin D2 ◽  
Dihydroxyvitamin D3 ◽  
Poor Renal Function

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P < 0.005 and P < 0.05, respectively) but no difference was seen in controls. 2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. 3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P < 0.02) but concentrations in the two groups were not different. 4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P < 0.05). 5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P < 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). 6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. 7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

Metabolic Support of Chloride-dependent Short-circuit Current Across Locust Rectum

1982 ◽  
Vol 99 (1) ◽  
pp. 349-362
Author(s):  
M. CHAMBERLIN ◽  
J. E. PHILLIPS
Keyword(s):  
Cyclic Amp ◽  
Short Circuit ◽  
Malpighian Tubule ◽  
Short Circuit Current ◽  
Metabolic Substrates ◽  
Endogenous Substrates ◽  
Tubule Fluid ◽  
Substrate Source ◽  
Stimulation Of

1. Recta of desert locusts were short-circuited and depleted of endogenous substrates by exposing them to saline containing cyclic AMP but no metabolites. Individual substrates were then added to substrate-depleted recta and the change in short-circuit current (Isc) monitored. 2. Proline or glucose (50 mM) caused by far the largest increase in Isc of all substrates tested. Stimulation of the Isc by proline was not dependent upon external sodium, but did require external chloride. 3. Physiological levels of proline also caused a large increase in Isc, while physiological levels of glucose produced a much smaller stimulation. Over 90% of the proline-dependent Isc stimulation can be produced by adding 15 mM proline solely to the lumen side of the tissue. 4. These results are discussed with regard to rectal oxidative metabolism and availability of metabolic substrates in vivo. High levels of proline in Malpighian tubule fluid are probably the major substrate source for rectal Cl−transport. Note:

Intestinal absorption of calcium: role of dietary phosphate and vitamin D

1981 ◽  
Vol 241 (1) ◽  
pp. G49-G53
Author(s):  
N. Brautbar ◽  
B. S. Levine ◽  
M. W. Walling ◽  
J. W. Coburn
Keyword(s):  
Vitamin D ◽  
Intestinal Absorption ◽  
Vitamin D3 ◽  
Control Groups ◽  
Dihydroxyvitamin D3 ◽  
Dietary Phosphorus ◽  
P Concentration ◽  
Dietary Phosphate ◽  
Intestinal Ca Absorption

The intestinal absorption of calcium (Ca) has been shown to depend on vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and dietary phosphorus (P) concentration. This study was designed to evaluate the role of dietary P independent of vitamin D3 or 1,25(OH)2D3. Vitamin D-deficient rats were studied during dietary P restriction and were compared with control groups raised on a normal-phosphorus diet (NP). Balance studies were sued. Net intestinal Ca absorption was significantly lower with dietary P restriction compared with the NP group. This malabsorption of Ca was corrected by the administration of either D3 for 1,25(OH)2D3, despite hypophosphatemia. Everted gut sacs showed a marked reduction in the uptake of 45Ca in the duodenum, jejunum, and ileum during dietary P restriction. We concluded that dietary P concentration plays a major role in intestinal Ca absorption in the vitamin D-deficient rats. These findings suggest an effect of the low-phosphate diet on the vitamin D-dependent, Ca-transport mechanism.

scholarly journals Epimers of Vitamin D: A Review

2020 ◽  
Vol 21 (2) ◽  
pp. 470 ◽  
Author(s):  
Bashar Al-Zohily ◽  
Asma Al-Menhali ◽  
Salah Gariballa ◽  
Afrozul Haq ◽  
Iltaf Shah
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Hydroxyl Group ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
In Vivo Models ◽  
Vitamin D Receptors ◽  
Potential Factors

In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC–MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC–MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.

Sign in / Sign up

Export Citation Format

Share Document