Vitamin D receptors in heart: effects on atrial natriuretic factor.

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D3 (1,25-D3, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D3 suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D3 and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.     

Distribution of the 1,25 dihydroxy-vitamin D3 receptor in the bursa of Fabricius of chicken

The vitamin D₃ metabolite 1,25(OH)₂D₃ is probably involved in B lymphocyte ontogeny. We therefore determined the distribution of the 1,25(OH)₂D₃ receptor in the bursa of Fabricius and spleen cells of 7-day-old chicks, by immunohistochemistry using a monoclonal antibody against the chick intestinal cell 1,25(OH)₂D₃ receptor. The bursa cells of young (7-day-old) chicks contained large amounts of receptor while the spleen cells did not. The bursa cells of older (35-day-old) chicks contained fewer receptors, but the number of receptors in the spleen increased.     

Atrial natriuretic factor in hypovolemic tachycardia

Summary Atrial natriuretic factor (ANF) is released in response to many stimuli which increase right atrial pressure. Following hemorrhage pigs lowered their atrial pressures, developed a tachycardia and increased ANF levels. Electrical pacing increased heart rate and ANF levels. There is a stimulus to ANF release other than atrial stretch, probably heart rate.     

Atrial natriuretic factor in hypovolemic tachycardia

Atrial natriuretic factor (ANF) is released in response to many stimuli which increase right atrial pressure. Following hemorrhage pigs lowered their atrial pressures, developed a tachycardia and increased ANF levels. Electrical pacing increased heart rate and ANF levels. There is a stimulus to ANF release other than atrial stretch, probably heart rate.     

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney,one-clip renal hypertension

Summary The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n=11) or a regular-sodium diet (n=10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.     

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney, one-clip renal hypertension

The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n = 11) or a regular-sodium diet (n = 10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.     

Distribution of the 1,25 dihydroxy-vitamin D3 receptor in the bursa of Fabricius of chicken.

The vitamin D3 metabolite 1,25(OH)2D3 is probably involved in B lymphocyte ontogeny. We therefore determined the distribution of the 1,25(OH)2D3 receptor in the bursa of Fabricius and spleen cells of 7-day-old chicks, by immunohistochemistry using a monoclonal antibody against the chick intestinal cell 1,25(OH)2D3 receptor. The bursa cells of young (7-day-old) chicks contained large amounts of receptor while the spleen cells did not. The bursa cells of older (35-day-old) chicks contained fewer receptors, but the number of receptors in the spleen increased.     

Responses of monkey,rabbit and dog internal carotid arteries to atrial natriuretic factor

Summary Effects of atrial natriuretic factor (ANF) on monkey, rabbit and dog internal carotid arteries were investigated. ANF caused a concentration-dependent relaxation in arterial strips submaximally precontracted with noradrenaline, 5-hydroxytryptamine, or high-potassium solution (10–30 mM). The response was greatest in the monkey arteries and least in the dog arteries. These results suggest that there is a marked species difference in the ANF-induced relaxation of the internal carotid arteries.     

Responses of monkey, rabbit and dog internal carotid arteries to atrial natriuretic factor

Effects of atrial natriuretic factor (ANF) on monkey, rabbit and dog internal carotid arteries were investigated. ANF caused a concentration-dependent relaxation in arterial strips submaximally precontracted with noradrenaline, 5-hydroxytryptamine, or high-potassium solution (10-30 mM). The response was greatest in the monkey arteries and least in the dog arteries. These results suggest that there is a marked species difference in the ANF-induced relaxation of the internal carotid arteries.     

The action of various vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryo calvariae

Summary Chick embryos from vitamin D-deficient hens given physiological doses of 1,25-dihydroxyvitamin D₃ or 24,25-dihydroxyvitamin D₃ or both become severely hypocalcemic, hyperphosphatemic and fail to hatch as compared to those derived from hens given 25-hydroxyvitamin D₃ or 24,25-difluoro-25-hydroxyvitamin D₃. Calvariae from the former contain less mineral and on incubation in vitro produce significantly lower calcium and higher phosphate concentration in the medium than do the calvariae derived from the embryos of hens supported on 25-hydroxyvitamin D₃ or 24,24-difluoro-25-hydroxyvitamin D₃.     

Drug susceptibility of PCA in WBB6F1-W/Wv mice

Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be produced in congenitally mast cell-deficient WBB6F1-W/W^v (abbreviated as W/W^v) mice on sensitization with undiluted or slightly diluted allogeneic and xenogeneic antisera but not on sensitization with allogeneic monoclonal immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration [1]. In view of these findings, the present study was conducted to characterize PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1-+/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/W^v mice mediated by a low dilution (1  4) of hyperimmune serum to bovine serum albumin of the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of platelet-activating factor (PAF), but not by antihistamines such as cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by a high dilution (1  128) of the anti-serum (virtually by IgG1 antibody) was nearly completely suppressed by antihistamines but not by CV-6209. A remarkable difference between PCA in W/W^v and reference mice was also observed in the susceptibility to monoclonal anti mouse granulocyte (Gr-1) antibody PCA in W/W^v mice was potently suppressed by the 1- to 3-day pretreatment with this antibody but that in references was not at all. Putting these present results together with the previous finding that anti-granulocyte antibody greatly reduces circulatory Gr-1⁺ leukocytes, 1 to 3 days after the treatment [2], it is highly probable that PCA in W/W^v mice mediated by some antibody isotypes other than IgE and IgG1 is produced by PAF mainly released from Gr-1⁺ cells, while IgG1 antibody-mediated PCA in mast cell-bearing reference mice is evoked by histamine derived from mast cells. PCA homologous to that in W/W^v mice could also be produced in the reference mice on sensitization with undiluted or slightly diluted antiserum, when generalized blueing due to excess IgG1 antibody was removed by the oxatomide treatment be fore the antigen challenge. Received 10 December 1997; received after revision 2 February 1998; accepted 23 February 1998     

Confirmation of sex pheromone biosynthesis from (16-D3)palmitic acid in the turnip moth using capillary gas chromatography

Summary (16-D₃)palmitic acid was applied topically to pheromone glands of the turnip moth. After incubation omega labeled analogues of fatty acid methyl esters and acetates were identified by gas chromatography with flame ionization detection and selected ion monitoring. The pheromone components (Z)-5-decenyl, (Z)-7-dodecenyl- and (Z)-9-tetradecenyl acetate were all biosynthesized from palmitic acid along a common pathway.     

The role of parathyroid hormone and calcitonin in magnesium absorption in the rat small intestine

Summary We studied duodenal and ileal magnesium (Mg) absorption in intact, parathyroidectomized (PTX), thyroid-(TX) and thyroparathyroidectomized (TPTX) rats with iodine hormones replaced, and, additionally, in PTX rats receiving bovine parathyroid hormone 1–34 and 1,25-dihydroxyvitamin D₃, respectively. Ma absorption was reduced after PTX and TPTX in the duodenum, but not in the ileum, whereas TX had no influence on duodenal or ileal Mg absorption. Both bovine parathyroid hormone 1–34 and 1,25-dihydroxyvitamin D₃ increased Mg absorption in the duodenum and the ileum in PTX rats.Acknowledgments. We are grateful to B. Schreiber, K. Schwille and I. Goldberg for technical and secretarial help. Supported by Deutsche Forschungsgemeinschaft (Schw 210/3). Reprint requests to P.O.S., University Hospital, Maximiliansplatz, D-8520 Erlangen.     

Efficacy of tumor cell vaccine after incorporating monophosphoryl lipid A (MPL) in tumor cell membranes containing tumor-associated ganglioside

Murine B16 melanoma expresses the ganglioside. GM₃. GM₃ shed from tumor cells is immunosuppressive and promotes tumor growth¹. Reduction or elimination of the shed GM₃ could be therapeutic, and the anti-GM₃ antibodies may reduce and clear the shed ganglioside. To test this hypothesis, mice were challenged with tumor cells, with or without inducing anti-GM₃ antibody response. Since gangliosides are poor immunogens and T-cell independent antigens, an adjuvant (monophosphoryl lipid A (MPL), a non-toxic lipid A ofSalmonella), directed against B-cells, was employed. MPL was incorporated onto liposomes and into the surface membrane of B16 mouse melanoma cells; both are rich in GM₃. C57BL/6J mice immunized with MPL-liposomes or MPL-B16 cells responded with elevated levels of anti-GM₃ IgM. Non-immunized mice or mice immunized with B16 cells alone or ganglioside GM₃ alone (without MPL) elicited poor anti-GM₃ IgM response, confirming the GM₃'s immunologic crypticity and MPL's immunopotentiating effect. MPL's immunopotentiating effect was improved by coupling it to melanoma cell membranes C57BL/6J mice were immunized with irradiated B16 alone or MPL alone or MPL-conjugated irradiated B16. After three weekly immunizations, each mouse received a challenge dose of viable syngeneic B16. Neither MPL alone nor B16 alone had a significant effect on tumor growth or host survival; however, administration of MPL-conjugated B16 cells significantly prevented tumor growth and prolonged survival. Our results indicate that MPL-incorporated B16 cells augment the anti-GM₃ IgM response, which may reverse GM₃-induced immunosuppression by eliminating tumor-derived GM₃, and restore immunocompetence.     

Lack of influence of vitamin D deficiency on insulin release from the isolated pancreatic islets of rats

Pancreatic islets were isolated from young (100 g) and adult (390 g), normal and vitamin D deficient male Sprague-Dawley rats. The release of insulin from leucine-stimulated or glucose-stimulated islet was not altered by vitamin D deficiency. The in vitro addition of either 25-hydroxy- or 1,25-dihydroxyvitamin-D had no effect on insulin release from either normal or vitamin D deficient islets. We conclude that the earlier report (Normal et al., Science 209 (1980) 823-825) on vitamin D deficiency depressing insulin secretion from the perfused pancreas must be related to the vitamin's effect on insulin synthesis and not the islet's release of insulin.     

Reversible depression of spontaneous brain electrical activity induced by actinomycin D and 7-aminoactinomycin D in rats

Summary Various types of actinomycin (C, D, S₂, I and V) and 7-amino-analogue of actinomycin D were injected into the right lateral ventricle of the brain through a chronically implanted cannula. In rats but not in mice actinomycin D, actinomycin S₂ and 7-aminoactinomycin D caused depression of EEG, while cardiac and respiratory activity were maintained. This effect of the EEG was reversible and a normal EEG pattern reappeared at least 3 h after administration.     

A survey of 3-dehydroretinal as a visual pigment chromophore in various species of crayfish and other freshwater crustaceans

Summary 3-Dehydroretinal (vitamin A₂ aldehyde) was found in the eyes of three species among 10 species of freshwater crayfish examined. Since dark-adapted eyes contained the 11-cis form of 3-dehydroretinal, this compound must be the chromophore of the visual pigment. 3-Dehydroretinal always coexisted with retinal (vitamin A₁ aldehyde), indicating the presence of a rhodopsin-porphyropsin visual pigment system.     

The action of various vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryo calvariae

Chick embryos from vitamin D-deficient hens given physiological doses of 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 or both become severely hypocalcemic, hyperphosphatemic and fail to hatch as compared to those derived from hens given 25-hydroxyvitamin D3 or 24,25-difluoro-25-hydroxyvitamin D3. Calvariae from the former contain less mineral and on incubation in vitro produce significantly lower calcium and higher phosphate concentration in the medium than do the calvariae derived from the embryos of hens supported on 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3.