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Biomedical subjects

M W Walling

Publications and source records attributed to M W Walling.

At least 37 records · Page 2Linked to original sources
PubMed1977

Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites.

The transport of Ca and inorganic phosphate (Pi) was studied in the absence of electrochemical gradients across rat intestine in vitro. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the active absorption of both Ca and Pi in all segments of the small intestine, with changes occurring only in absorptive fluxes, whereas secretory fluxes were unaffected. Active Ca absorption was greatest in the duodenum (greater than jejunum greater than ileum) and active Pi absorption was highest in jejunum (greater than duodenum greater than ileum), in agreement with earlier reports. 24R,25-dihydroxy-vitamin2D3 had similar effects on transport but was less potent. The ratios of Pi absorptive fluxes to Ca absorptive fluxes remained remarkably constant during 80-200% increases in absorption produced by 1,25(OH)2D3, suggesting coupled Ca-Pi transport or coordinate stimulation of Ca and Pi absorptive processes by hormonally active metabolites of vitamin D. The results seem most compatible with a differential distribution of vitamin D-responsive Ca and Pi absorptive cells with a predominance of cells with Ca absorptive sites occurring in duodenum, more Pi absorbing cells in jejunum, and a nearly equal ratio of each type in ileum.

Animals↗
PubMed1977

Effects of calcitonin and substance P on the transport of Ca, Na and Cl across rat ileum in vitro.

Both salmon calcitonin (SCT) and substance P decreased ileal Na absorption, changed Cl transport from net absorption to net secretion and elevated the short circuit current when added in vitro at concentrations of 10 microng per ml to solutions bathing the serosal surface of rat ileum which had been stripped of its serosal muscle coat. The effects of substance P were of greater magnitude but shorter duration than SCT. Both peptides also increased the bidirectional fluxes of Ca but did not alter net Ca movement. The changes in Na and Cl fluxes and short circuit current are identifical to those which occur when cellular levels of cyclic AMP increased. However, incubation of ileal mucosa with SCT or substance P did not cause a detectable change in cellular levels of cyclic AMP or cyclic GMP. Both the mechanism of action and the possible physiological functions of SCT and substance P in the regulation of electrolyte transport require further investigation. The results with SCT appear to confirm prior suggestions that calcitonin may act directly to produce secretory diarrhea under pathophysiological conditions.

Animals↗
PubMed1976

Duodenal active transport of calcium and phosphate in vitamin D-deficient rats: effects of nephrectomy, Cestrum diurnum, and 1alpha,25-dihydroxyvitamin D3.

Both the methanol:chloroform extractable material from the leaves of the Solanaceous plant, Cestrum diurnum (C.d.), and a 270 ng dose of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) increased the active absorption of calcium and phosphate across the proximal duodenum, studied in vitro, from sham-operated and nephrectomized (NPX) vitamin D-deficient rats. In these studies, conducted 24 h after surgery, the uremic state in the NPX animals markedly diminished the intestinal transport response to 1alpha,25-(OH)2D3 and also lowered baseline transport values across duodenum from the NPX vitamin D-deficient controls. Both C.d. and 1alpha, 25-(OH)2D3 elevated plasma Ca levels equally well in the sham-operated and NPX groups. The stimulation of intestinal Ca absorption in NPX animals indicates that, like the leaves of the South American plant, Solanum glaucophyllum, C.d. contains materials which can function in an analogous manner to compounds in the vitamin D group that have either a 1alpha hydroxyl group or its steric equivalent.

Animals↗
PubMed1976

Elevation of cyclic AMP levels and adenylate cyclase activity in duodenal mucosa from vitamin D-deficient rats by 1alpha,25-dihydroxycholecalciferol (1alpha,25-(OH)2D3).

A single 270 ng dose of 1alpha,25-(OH2D3 rpoduced 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 1alpha,25-(OH)2D3 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 1alpha,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 1alpha,25-(OH)2D3 administration, and to determine the role, if any, of this nucleotide in the hormones' effect on intestinal calcium absorption.

Adenylyl Cyclases↗
PubMed1975

Active secretion of calcium, sodium and chloride by adult rat duodenum in vitro.

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+.

Animals↗
PubMed1975

Effects of 1alpha,25-dihydroxyvitamin D3 and Solanum glaucophyllum on intestinal calcium and phosphate transport and on plasma Ca, Mg and P levels in the rat.

The responses elicited by a single dose of either S. glaucophyllum (SG) or 1alpha,25-dihydroxyvitamin D3 (1alpha, 25-(OH)2D3) in vitamin D-deficient rats were qualitatively identical. Both compounds stimulated duodenal absorption of calcium and phosphate 3 h after administration, and the effects persisted for 96 h. The SG effects on calcium transport were maximal at 6 h and exceeded the greatest response to 1alpha,25-(OH)2D3 which occurred at 48 h. While the early SG effects on phosphate absorption exceeded those of 1alpha,25-(OH)2D3, the latter compound had a much greater effect at 48 h. Both SG and 1alpha, 25-(OH)2D3 produced marked hyperphosphatemia that was accompanied by hypocalcemia and transient hypermagnesemia at 3-6 h. The phosphatemia increased for 48 h in the 1alpha,25-(OH)2D3 group and fell toward baseline between 48 and 96 h, while this parameter was maximal in the SG group at 3-12 h and returned to baseline values by 96 h. Plasma calcium levels tended to vary inversely with phosphorus concentrations and did not exceed baseline values until 48 h for the SG group and 96 h for the 1alpha,25-(OH)2D3 group. We suggest that the hypocalcemia is due to calcium phosphate precipitation. The quantitative differences in the effects on calcium and phosphorus metabolism may be dose-related. The responses to SG suggest that a gram of dried leaf has approximately the same activity as 1 mug of 1alpha,25-(OH)2D3. It appears that the water-soluble SG factor has the same biological effects on Ca and P metabolism as does 1alpha,25-(OH)2D3.

Animals↗
PubMed1975

Effects of magnesium deficiency and thyroparathyroidectomy on calcium active transport by rat duodenum.

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 aminals fed a Mg-containing 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 hypomagnesemia 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.

Animals↗
PubMed1975

Calcium absorption by intestine. Stimulation in vitamin D-deficient nephrectomized rats by Solanum glaucophyllum.

The administration of an aqueous extract made from leaves of the South American plant Solanum glaucophyllum increased active duodenal calcium absorption 6-fold in sham operated vitamin D-deficient rats and 4.5-fold in comparable animals that had been nephrectomized. These results demonstrate that the active principle from the plant does not require renal metabolism for effects on intestinal calcium absorption, a biological activity previously observed only with sterols such as 1,25-dihydroxyvitamin D3 which have a 1-alpha hydroxyl group or a steric equivalent. The similarity of action between these lipid soluble sterols and the water soluble plant material may be explained by the presence of glycosidal alkaloidal steroids in plants from the genus Solanum.

Alkaline Phosphatase↗
PubMed1974

Effects of dietary calcium restriction and chronic thyroparathyroidectomy on the metabolism of (3H)25-hydroxyvitamin D3 and the active transport of calcium by rat intestine.

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.

Animals↗
PubMed1973

Effects of 1,25-dihydroxycholecalciferol on intestinal calcium transport in cortisone-treated rats.

The administration of glucocorticoids may decrease intestinal calcium absorption in vivo and the active transport of calcium in rat duodenum in vitro. It has been suggested that this apparent "anti-vitamin D-like" effect of steroid hormones may be related to alterations in vitamin D metabolism. In order to test this hypothesis, vitamin D-deficient control and cortisone-treated rats were given an intraperitoneal injection of 5.5 IU of 1,25-dihydroxycholecalciferol (1,25-DHCC), the probable end-organ active vitamin D metabolite in the intestine, and 16 h later studies of duodenal calcium transport were performed in modified Ussing chambers. In the vitamin D-deficient state, cortisone administration was associated with a diminution in J(MS), J(Net), and the flux ratio (J(MS)/J(SM)). While the magnitude of the increases in J(MS) and J(Net) that resulted from 1,25-DHCC treatment were approximately the same in control and cortisone-treated animals, 1,25-DHCC failed to restore these parameters to "normal levels" in the steroid-treated rats. Furthermore, contrary to the results obtained in the saline-treated controls, 1,25-DHCC failed to reduce J(SM) in the duodenum from cortisone-treated rats. The cortisone-related defect in calcium transport was due to alterations in both unidirectional calcium fluxes (decrease in J(MS) and increase in J(SM)), such that the J(Net) and the flux ratio (J(MS)/J(SM)) were only approximately 50% of the levels achieved in vitamin D-deficient control animals repleted with the same dose of 1,25-DHCC. The administration of 1,25-DHCC was accompanied by a marked increase in the serum calcium levels of control rats, but there was no such response in the cortisone-treated group. The results support the concept that under the conditions of these experiments in the rat the apparent antagonism between glucocorticoids and vitamin D may be due to steroid hormone-related alterations in end organ function that are independent of any direct interaction between the hormone and the vitamin and that cannot be reversed by the vitamin.

Animals↗