Effects of vitamin D3, 25(OH) vitamin D3, 24,25(OH)2 vitamin D3, and 1,25(OH)2 vitamin D3 on the in vitro intestinal calcium absorption in the marine teleost, Atlantic cod (Gadus morhua)

1990 ◽  
Vol 78 (1) ◽  
pp. 74-79 ◽  
Author(s):  
Kristina Sundell ◽  
Björn Th. Björnsson
Keyword(s):  
Vitamin D3 ◽  
Gadus Morhua ◽  
Calcium Absorption ◽  
Atlantic Cod ◽  
Intestinal Calcium Absorption ◽  
Marine Teleost

scholarly journals Kinetics of Calcium Fluxes Across the Intestinal Mucosa of the Marine Teleost, Gadus Morhua, Measured Using an In Vitro Perfusion Method

1988 ◽  
Vol 140 (1) ◽  
pp. 171-186 ◽  
Author(s):  
KRISTINA SUNDELL ◽  
BJÖRN THRANDUR BJÖRNSSON
Keyword(s):  
Intestinal Mucosa ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Calcium Influx ◽  
Calcium Excretion ◽  
Passive Component ◽  
Marine Teleost ◽  
Atpase Inhibitor

An in vitro technique for perfusion of the intestinal vasculature and lumen was developed and used to measure calcium (Ca2+) fluxes across the intestinal mucosa of the marine teleost, the Atlantic cod (Gadus morhua). Saturable and nonsaturable components of the calcium influx and efflux were determined. The calcium influx had one passive component and one saturable component, following Michaelis-Menten kinetics with Km = 8.41mmoll−1 and Vmax = 0.604μmol Ca2+ kg−1 h−1. At physiological Ca2+ concentrations in the vascular ([Ca2+] = l.9mmoll−1) and luminal ([Ca2+] =14.9mmoll−1) perfusion fluids, the saturable component amounted to 60% of the Ca2+ influx. The high-affinity Ca2+-ATPase inhibitor chlorpromazine (CP, 10−4moll−1) antagonized 45% of the Ca2+ influx. The Ca2+ efflux across the intestinal mucosa of the cod was a saturable process, following Michaelis-Menten kinetics with Km =6.15mmoll−1 and Vmax =3.79μmol Ca2+ kg−1h−1, but insensitive to CP (l0−5moll−1). The Ca2+ efflux was l.22μumol Ca2+ kg−1 h−1, representing about 20% of the total calcium excretion and about 50% of the extrarenal excretion of the Atlantic cod in vivo.

scholarly journals Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 82-93 ◽  
Author(s):  
JY Zhou ◽  
AW Norman ◽  
M Lubbert ◽  
ED Collins ◽  
MR Uskokovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mechanism Of Action ◽  
Vitamin D3 ◽  
Clonal Growth ◽  
Calcium Absorption ◽  
Active Form ◽  
Intestinal Calcium Absorption ◽  
Leukemic Cells ◽  
Binding Studies ◽  
Vitamin D Analogs

Abstract Induction of terminal differentiation of leukemic and preleukemic cells is a therapeutic approach to leukemia and preleukemia. The 1 alpha, 25- dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form of vitamin D3, can induce differentiation and inhibit proliferation of leukemia cells, but concentrations required to achieve these effects cause life-threatening hypercalcemia. Seven new analogs of 1,25(OH)2D3 were discovered to be either equivalent or more potent than 1,25(OH)2D3 as assessed by: (a) inhibition of clonal proliferation of HL-60, EM-2, U937, and patients' myeloid leukemic cells: and (b) induction of differentiation of HL-60 promyelocytes. Furthermore, these analogs stimulated clonal growth of normal human myeloid stem cells. The most potent analog, 1,25-dihydroxy-16ene-23yne-vitamin D3, was about fourfold more potent than 1,25(OH)2D3. This analog decreased clonal growth and expression of c-myc oncogene in HL-60 cells by 50% within ten hours of exposure. Effects on calcium metabolism of these novel analogs in vivo was assessed by intestinal calcium absorption (ICA) and bone calcium mobilization (BCM). Each of the analogs mediated markedly less (10 to 200-fold) ICA and BCM as compared with 1,25(OH)2D3. To gain insight into the possible mechanism of action of these new analogs, receptor binding studies were done with 1,25(OH)2–16ene-23yne-D3 and showed that it competed only about 60% as effectively as 1,25(OH)2D3 for 1,25(OH)2D3 receptors present in HL-60 cells and 98% as effective as 1,25(OH)2D3 for receptors present in chick intestinal cells. In summary, we have discovered seven novel vitamin D analogs that are more potent than the physiologic 1,25(OH)2D3 as measured by a variety of hematopoietic assays. In contrast, these compounds appear to have the potential to be markedly less toxic (induction of hypercalcemia). These novel vitamin D compounds may be superior to 1,25(OH)2D3 in a number of clinical situations including leukemia/preleukemia; they will provide a tool to dissect the mechanism of action of vitamin D seco-steroids in promoting cellular differentiation.

Steroid Transformations by Corpuscles of Stannius of the Atlantic Cod (Gadus morhua L.)

1966 ◽  
Vol 23 (8) ◽  
pp. 1249-1255 ◽  
Author(s):  
D. R. Idler ◽  
H. C. Freeman
Keyword(s):  
Gadus Morhua ◽  
Atlantic Cod ◽  
Hydroxysteroid Dehydrogenase ◽  
Corpuscles Of Stannius

Corpuscles of Stannius tissue of Atlantic cod (Gadus morhua L.) transformed [4-14C] pregnenolone to progesterone and [4-14C] progesterone to 11-desoxycorticosterone in vitro. These results establish the presence of 3β-hydroxysteroid dehydrogenase, Δ5-3-ketoisomerase and 21-hydroxylase. Transformation of the 14C-steroid precursors to several as yet unidentified substances also occurred.

Development of a novel 1,25(OH)2-vitamin D3 analog with potent ability to induce HL-60 cell differentiation without modulating calcium metabolism

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 75-82 ◽  
Author(s):  
JY Zhou ◽  
AW Norman ◽  
M Akashi ◽  
DL Chen ◽  
MR Uskokovic ◽  
...  
Keyword(s):  
Vitamin D3 ◽  
Calcium Metabolism ◽  
Calcium Absorption ◽  
Leukemic Cells ◽  
Inhibition Of Proliferation ◽  
Myc Oncogene ◽  
Differentiation And Proliferation ◽  
Bone Abnormalities

We describe several novel analogs of the seco-steroid 1,25(OH)2-vitamin D3[1,25(OH)2D3] and their effects on differentiation and proliferation of HL-60 human myeloid leukemic cells in vitro as well as their effects on calcium metabolism in vivo. The 1 alpha-25(OH)2–16ene-23yne-26,27F6- vitamin D3 is the most potent analog reported to date, having about 80- fold more activity than the reference 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of HL-60 cells. Also, this analog decreased RNA expression of MYC oncogene in HL-60 by 90% at 5 x 10(-10) mol/L. Intriguingly, intestinal calcium absorption and bone calcium mobilization mediated in vivo by 1 alpha-25(OH)2–16ene-23yne- 26,27F6-D3 was found to be markedly (15-fold) less than that of 1,25(OH)2D3. In addition, 1 alpha-25(OH)2D3 bound to 1,25(OH)2D3 receptors of both HL-60 and intestine more avidly than did 1 alpha- 25(OH)2–16ene-23yne-26,27F6-D3. This novel analog may open up new therapeutic strategies for several hematopoietic, skin, and bone abnormalities and may provide a new tool to understand how vitamin D3 seco-steroids induce cellular differentiation.

scholarly journals Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 82-93 ◽  
Author(s):  
JY Zhou ◽  
AW Norman ◽  
M Lubbert ◽  
ED Collins ◽  
MR Uskokovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mechanism Of Action ◽  
Vitamin D3 ◽  
Clonal Growth ◽  
Calcium Absorption ◽  
Active Form ◽  
Intestinal Calcium Absorption ◽  
Leukemic Cells ◽  
Binding Studies ◽  
Vitamin D Analogs

Induction of terminal differentiation of leukemic and preleukemic cells is a therapeutic approach to leukemia and preleukemia. The 1 alpha, 25- dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form of vitamin D3, can induce differentiation and inhibit proliferation of leukemia cells, but concentrations required to achieve these effects cause life-threatening hypercalcemia. Seven new analogs of 1,25(OH)2D3 were discovered to be either equivalent or more potent than 1,25(OH)2D3 as assessed by: (a) inhibition of clonal proliferation of HL-60, EM-2, U937, and patients' myeloid leukemic cells: and (b) induction of differentiation of HL-60 promyelocytes. Furthermore, these analogs stimulated clonal growth of normal human myeloid stem cells. The most potent analog, 1,25-dihydroxy-16ene-23yne-vitamin D3, was about fourfold more potent than 1,25(OH)2D3. This analog decreased clonal growth and expression of c-myc oncogene in HL-60 cells by 50% within ten hours of exposure. Effects on calcium metabolism of these novel analogs in vivo was assessed by intestinal calcium absorption (ICA) and bone calcium mobilization (BCM). Each of the analogs mediated markedly less (10 to 200-fold) ICA and BCM as compared with 1,25(OH)2D3. To gain insight into the possible mechanism of action of these new analogs, receptor binding studies were done with 1,25(OH)2–16ene-23yne-D3 and showed that it competed only about 60% as effectively as 1,25(OH)2D3 for 1,25(OH)2D3 receptors present in HL-60 cells and 98% as effective as 1,25(OH)2D3 for receptors present in chick intestinal cells. In summary, we have discovered seven novel vitamin D analogs that are more potent than the physiologic 1,25(OH)2D3 as measured by a variety of hematopoietic assays. In contrast, these compounds appear to have the potential to be markedly less toxic (induction of hypercalcemia). These novel vitamin D compounds may be superior to 1,25(OH)2D3 in a number of clinical situations including leukemia/preleukemia; they will provide a tool to dissect the mechanism of action of vitamin D seco-steroids in promoting cellular differentiation.

scholarly journals The Effect of Vitamin D2 and Vitamin D3 on Intestinal Calcium Absorption in Nigerian Children with Rickets

2009 ◽  
Vol 94 (9) ◽  
pp. 3314-3321 ◽  
Author(s):  
Tom D. Thacher ◽  
Michael O. Obadofin ◽  
Kimberly O. O'Brien ◽  
Steven A. Abrams
Keyword(s):  
Vitamin D3 ◽  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Vitamin D2 ◽  
Nigerian Children
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