Marlin W. Walling
Beth Israel Deaconess Medical Center
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Journal of Clinical Investigation | 1974
Murray J. Favus; Marlin W. Walling; Daniel V. Kimberg
Previous studies have shown that chronically thyroparathyroidectomized (TPTX) rats, fed a diet with restricted calcium but adequate phosphorus and vitamin D content, have higher levels of intestinal calcium absorption than controls. The results of recent acute experiments have suggested that parathyroid hormone (PTH) may be essential for regulating the renal conversion of 25-hydroxyvitamin D(3) (25-OH-D(3)) to 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)-D(3)] in response to dietary calcium deprivation. Since 1,25-(OH)(2)-D(3) is the form of the vitamin thought to be active in the intestine, increases in calcium transport mediated by this metabolite would not be expected to occur in the absence of the parathyroid glands if the preceding model is correct. The present study was undertaken to examine the chronic effects of both dietary calcium restriction and the absence of PTH on the metabolism of [(3)H]25-OH-D(3) and duodenal calcium-active transport in rats given thyroid replacement. These relatively long term studies confirm earlier observations which indicated that the adaptation of calcium absorption to a low calcium intake occurs in both sham-operated and TPTX animals. The present studies also demonstrated that despite reduced levels of 1,25-(OH)(2)-D(3) in the plasma of chronically TPTX animals fed a low calcium diet, the accumulation of this metabolite in at least one target tissue, intestinal mucosa, is identical in both the sham-operated and TPTX groups. A reduced, but continued level of 1,25-(OH)(2)-D(3) production, together with its selective accumulation by intestinal mucosa, probably explains the calcium adaptation which is observed inspite of the chronic absence of the parathyroid glands.
Journal of Clinical Investigation | 1979
Nachman Brautbar; Marlin W. Walling; Jack W. Coburn
To evaluate the role of vitamin D in the physiologic response to phosphorus depletion (P depleton) and the response to vitamin D administration in P depletion, we studied vitamin D-deficient (-D) rats, fed either a normal or low phosphorus diet and then injected intraperitoneally on alternate days with replacement vitamin D(3), 1.25 mug qod (D(3)); 1.25-dihydroxy-vitamin D(3)[1,25(OH)(2)D(3)] in physiologic, 54 ng qod (LD), and pharmacologic doses, 400 ng qod (HD); or vehicle alone (-D). The following results were obtained: (a) With P depletion, urinary excretion of inorganic phosphorus (Pi) fell to almost undetectable levels in -D rats, and two physiologic features of P depletion a calcemic effect and hypercalciuria, ensued. (b) With administration of vitamin D(3) or 1,25(OH)(2)D(3) in either doses to P-depleted rats, the renal retention of Pi was unaltered despite a significant elevation of serum Pi. (c) The calcemic response to P depletion was accentuated by vitamin D sterols, and the hypercalciuria of P depletion was reduced by 1,25(OH)(2)D(3), HD > LD > D(3). (d) In -D animals receiving normal Pi (+P), D(3), and 1,25(OH)(2)D(3), both LD and HD produced a significant calcemic and phosphatemic effect. (e) Urinary Pi excretion in +P animals was reduced slightly by vitamin D(3) whereas 1,25(OH)(2)D(3), both LD and HD, lowered urinary Pi markedly despite an increased serum Pi. (f) The serial values of serum Ca and Pi and urinary Ca in PD rats and the sequential values for urinary and serum Pi in +P rats indicated more rapid effects of 1,25(OH)(2)D(3), both HD and LD, compared with D(3). We conclude that: (a) The renal adaptation and physiologic response to PD does not require the presence of vitamin D. (b) 1,25(OH)(2)D(3) may directly enhance the renal tubular reabsorption of Pi even as serum Pi rises. (c) A hypocalciuric action of 1,25(OH)(2)D(3) in rats on low phosphorus diet could be direct or occur as a consequence of an increase in serum Pi produced by 1,25(OH)(2)D(3). The different sequential renal response to D(3) compared with 1,25-(OH)(2)D(3) raises the possibility that other natural forms of vitamin D(3) [i.e., 25(OH)D(3), 24,25(OH)(2)D(3), etc.] which may be present in vitamin D-fed rats but not those given only 1,25(OH)(2)D(3), could modify the actions of 1,25(OH)(2)D(3).
Endocrine Research | 1976
Marlin W. Walling; Thomas A Brasitus; Daniel V. Kimberg
A single 270 ng dose of lα,25-(OH)2D3 produced elevations in cyclic AMP content and adenylate cyclase activity in duodenal mucosa from previously vitamin D-deficient rats. No changes in jejunal or ileal cyclic AMP levels or duodenal cyclic GMP levels were observed. Since lα,25-(OH)2 D3 increased both baseline and NaF-stimulated adenylate cyclase activity, it is possible that the vitamin leads to enhanced enzyme synthesis.While parallel changes in duodenal cyclic AMP levels and active calcium absorption in response to lα,25-(OH)2D3 were observed at 6,12,24 and 48 hr after treatment, increases in calcium absorption were observed at 3 hr in duodenum and at 48 hr in ileum in the absence of changes in cyclic AMP levels. Further studies will be required to determine whether or not the changes in duodenal cyclic AMP levels are direct or indirect effects of lα,25-(OH)2D3 administration, and to determine the role, if any, of this nucleotide in the hormones’ effect on intestinal calcium absorption.
Disorders of Mineral Metabolism#R##N#Calcium Physiology | 1982
Barton S. Levine; Marlin W. Walling; Jack W. Coburn
Publisher Summary The metabolism of calcium (Ca) is regulated in part via changes in its intestinal absorption. This chapter discusses the general aspects of Ca absorption, the methods for measuring overall intestinal absorption and the transport of Ca, and various hormonal and other factors that may alter Ca absorption. It also discusses the common physiologic events and clinical disorders that modify the intestinal Ca absorption. Unlike other elements in the diet, such as sodium and potassium, which are almost entirely absorbed, only a fraction of dietary Ca is absorbed by the intestine of adult humans. The net absorption of Ca represents the vectoral sum of two processes, the transfer of Ca from the intestinal lumen into the blood and the transfer of Ca from the plasma into the lumen. There are a number of factors that have a major effect on intestinal Ca absorption; thus, Ca absorption is much greater in children during periods of skeletal growth; on the other hand, Ca absorption decreases with advancing age. The fraction of intestinal Ca absorbed is known to increase in patients ingesting a diet low in Ca content; also, there are several hormones, agents, and constituents in the diet that may alter the intestinal absorption of Ca.
Biochimica et Biophysica Acta | 1975
Marlin W. Walling; Daniel V. Kimberg
Active secretion of Ca2+ is observed from the serosal to the mucosal surface across adult rat duodenum in vitro when absorptive Ca2+ flux is saturated by a high [Ca2+]. Sodium and chloride are spontaneously secreted by this tissue with Cl secretion apparently accounting for about one-third of the short-circuit current when there is no absorptive co-transport of Na+.
Experimental Biology and Medicine | 1975
Marlin W. Walling; Murray J. Favus; Daniel V. Kimberg
Summary Mg deficiency was produced in rats by feeding a Mg-free diet. Ten days of dietary Mg depletion led to an increase in active duodenal Ca absorption in sham-operated animals, but this increase was abolished by thyroparathyroidectomy (TPTX). In addition, TPTX reduced Ca absorption in control animals fed a Mg-con-taining diet. More prolonged Mg deficiency was produced by feeding sham-operated animals the Mg-free diet for 19 days. This condition resulted in more marked hypo-magnesemia and a depression of Ca transport rates to the level observed in the TPTX groups. These results are consistent with the concept that adaptation of duodenal Ca transport in response to Mg deficiency occurs through an increase in parathyroid hormone (PTH) secretion; however, direct blood PTH measurements will be required to prove this point. We would like to thank Gail Millar Fishbein for her expert technical assistance.
Journal of Clinical Investigation | 1973
Murray J. Favus; Marlin W. Walling; Daniel V. Kimberg
Endocrinology | 1975
Marlin W. Walling; Daniel V. Kimberg
Journal of Biological Chemistry | 1970
Marlin W. Walling; S. S. Rothman
Journal of Biological Chemistry | 1974
Marlin W. Walling; Murray J. Favus; Daniel V. Kimberg