PubMed Health⌕ Search

Biomedical subjects

A Tenenhouse

Publications and source records attributed to A Tenenhouse.

At least 19 recordsLinked to original sources
PubMed1988

Vitamin D and parotid gland function in the rat.

1. We previously reported that parotid gland secretion is decreased in rats deprived of vitamin D (Glijer, Peterfy & Tenenhouse, 1985). In the present study we examine whether this effect is a direct result of the absence of vitamin D or due to the secondary systemic effects of vitamin D deficiency. 2. Offspring of rats maintained on a calcium-supplemented (1.2%), vitamin-D-deficient diet were weaned onto the same diet and examined after 8 weeks. Using this method it was possible to maintain serum calcium and parathyroid hormone concentrations within normal limits. Serum 25-hydroxyvitamin D (25(OH)D3) was not detectable, but 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations were normal. 3. Pilocarpine-stimulated flow of parotid saliva was reduced 57% in vitamin-D-deprived animals, but amylase secretion was unchanged. Treatment with vitamin D3 returned flow rates to normal. 4. The concentration of calcium in parotid saliva was normal in vitamin-D-deprived rats, although total parotid calcium output was reduced 57%. 5. Pilocarpine-stimulated salivary flow from submandibular gland, a tissue which does not possess 1,25(OH)2D3 receptors, was normal in vitamin-D-deprived rats. 6. Heart rate and arterial blood pressure changes in response to I.V. pilocarpine administration were identical in normal and vitamin-D-deficient rats. 7. Auriculotemporal nerve-stimulated flow of parotid saliva was also reduced by 50% and administration of vitamin D3 to these rats corrected this abnormality. 8. It is concluded that fluid and electrolyte secretion from parotid gland is directly dependent on vitamin D; abnormal parotid gland function seen in vitamin-D-deficient rats is not due to secondary hypocalcaemia or hyperparathyroidism, nor can it be explained by haemodynamic changes evoked during systemic administration of pilocarpine. We further conclude that the metabolite of vitamin D responsible for this effect is not 1,25(OH)2D3.

Animals↗
PubMed1988

Parathyroid hormone desensitization in renal membranes of vitamin D-deficient rats is associated with a postreceptor defect.

We examined the characteristics of PTH resistance in vitamin D-deficient rats employing renal membranes in vitro. Homologous desensitization was characterized by diminished PTH-stimulated adenylate cyclase activity and was associated with a reduction in PTH-binding capacity, but not affinity. Heterologous desensitization was also seen, as manifested by decreased calcitonin (CT)-stimulated adenylate cyclase activity with normal CT receptor binding. The reduced capacity of the nonhormonal effectors NaF and guanylylimidodiphosphate to stimulate adenylate cyclase indicated a postreceptor defect at the level of the guanyl nucleotide-binding protein (G protein), whereas a normal forskolin response was consistent with a fully functional catalytic component. The G protein deficiency was confirmed by demonstrating that the addition of extracts of vitamin D-sufficient membranes to preparations of vitamin D-deficient membranes restored the normal responses to NaF and guanylylimidodiphosphate. In addition, cholera toxin- and pertussis toxin-catalyzed labeling of vitamin D-deficient renal membranes with [32P]NAD revealed a decrease in both the stimulatory and inhibitory binding proteins. Experiments with testicular membranes in vitro indicated that the adenylate cyclase abnormality was absent in tissue lacking PTH receptors. The results suggest that a major contribution to PTH resistance in vitamin D-deficient animals is a postreceptor defect at the level of the G proteins and that this defect is manifest only in tissue expressing the PTH receptor.

Adenosine Diphosphate Ribose↗
PubMed1985

The effect of vitamin D deficiency on secretion of saliva by rat parotid gland in vivo.

The role of vitamin D in parotid gland function was investigated by measuring the composition and rate of production of parotid saliva in response to pilocarpine injection in vitamin-D-deficient and replete rats in vivo. Rats fed a vitamin-D-free diet from weaning (G1) were studied after 8 weeks of diet at which time they had a decreased rate of growth, were hyperparathyroid and hypocalcaemic but still had detectable serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3). Rats which were the offspring of vitamin-D-deficient mothers and which were maintained on a vitamin-D-free diet from weaning (G2) had a decreased rate of growth from birth, were hypocalcaemic and hyperparathyroid and at no time had any detectable serum 1,25(OH)2D3. In response to pilocarpine, the volume of parotid saliva produced by G1 animals was no different from the controls (G1 animals receiving supplemental vitamin D) whereas that produced by G2 animals was reduced more than 65%. The total amount of amylase secreted was unchanged in either group of experimental animals so that the concentration of amylase in the parotid saliva from G2 animals was increased. The concentration of calcium in parotid saliva changed in parallel with the changes in serum calcium in G1 and G2 animals. It is concluded that the primary source of parotid saliva calcium is the extracellular fluid and not zymogen granules and the transepithelial transport of this calcium is independent of vitamin D; the secretion of electrolytes and water, which in the parotid gland require extracellular calcium, is dependent on vitamin D. It is proposed that the vitamin is necessary for the synthesis of a protein(s) which is essential for the utilization of extracellular calcium in this secretion process.

Amylases↗
PubMed1985

Regulation of renal vitamin D hydroxylase activity in vitamin D deficient rats.

The regulation of renal mitochondrial 1-hydroxylase activity in chronic vitamin D deficiency was studied in male rats. These rats were born of mothers who had been raised from weaning (21 days) on a vitamin D deficient diet and who had no detectable serum 1,25-dihydroxycholecalciferol (1,25-(OH)2D) at the time their offspring were weaned (28 days). In the pups, renal mitochondrial 1-hydroxylase activity was undetectable before the 3rd week of life even though the animals were severely hypocalcemic from birth. The 1-hydroxylase activity first became detectable at 26 days of age, rapidly reached a maximum at day 34, then decreased to become undetectable again by 65 days. Throughout this time serum calcium concentration was less than 5.0 mg/dL and serum parathyroid hormone (PTH) concentration, measured by a midmolecule radioimmunoassay, was two- to five-fold greater than that found in vitamin D replete rats. 1-Hydroxylase activity could be restored in the +65-day-old animals by administration of a single dose of 2.5 micrograms vitamin D3. Enzyme activity was detected within 24 h, was maximal at 72 h, and returned to undetectable levels by 96 h after administration of the vitamin. Serum 1,25-(OH)2D which was undetectable before administration of the vitamin D3, was 108 and 458 pg/mL at 16 and 40 h, respectively, after the injection. The serum concentration of this metabolite then decreased progressively to 80 pg/mL by 6 days. 24-Hydroxylase activity first became detectable 48 h after vitamin D administration, increased to a maximum at 96 h, and thereafter decreased to become undetectable by 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1984

Decarboxylation of L-dopa and 5-hydroxytryptophan in dispersed rat pancreas acinar cells.

Amino acid decarboxylation activity in dispersed rat pancreas acinar cells and fractions derived by differential centrifugation of homogenate of these cells was studied. The rate of decarboxylation was measured by determining the rate of production of the [3H]-amine from [3H]-amino acid or the rate of production of 14CO2 from the [14C]-carboxy-labelled amino acid. Only the hydroxylated amino acids L-dopa and 5-hydroxytryptophan are decarboxylated by intact dispersed pancreas acinar cells or cell homogenates at all pH values and amino acid concentrations tested. The decarboxylase activity is located exclusively in the cell cytosol. Each substrate competitively inhibits the decarboxylation of the other and the decarboxylation of each is inhibited by NSD-1055. The estimated Km and Vmax are, for L-dopa, 4.8 X 10(-5) M and 2.5 nmol/mg protein/min and for 5-hydroxytryptophan, 2.9 X 10(-5) M and 0.3 nmol/mg protein/min. The pH optimum for 5-hydroxytryptophan decarboxylation is from 7.0-8.5 while that for L-dopa is 7.0. It is concluded that pancreas acinar cells possess a single aromatic amino acid decarboxylase specific for the hydroxylated amino acids L-dopa and 5-hydroxytryptophan, and which is similar in all properties studied to the aromatic amino acid decarboxylase found in several other mammalian tissues.

Animals↗
PubMed1983

Uptake, storage and secretion of 5-hydroxytryptamine and its amino acid precursor by dispersed rat pancreas acinar cells.

Rat pancreas acinar cells contain 5-hydroxytryptamine (5-HT; 10.86 +/- 2.52 ng/i.u. amylase), all of which can be accounted for by the 5-HT recovered from the zymogen granule fraction of these cells (10.70 +/- 3.06 ng/i.u. amylase). When incubated with [14C]5-HT dispersed acinar cells take up the amine and concentrate it in zymogen granules. These cells will also take up [14C]5-HTP (5-hydroxytryptophan), decarboxylate it and store the [14C]5-HT so produced in zymogen granules. 5-HTP itself is not taken up by the granules. 5-HT is incorporated into zymogen granules early in their formation; no amine is accumulated by mature zymogen granules and the amine within the mature granule is not exchangeable with extragranular amine. When dispersed acinar cells pre-labelled with [14C]5-HT and [3H]leucine are stimulated with caerulein, there is a synchronous increase in amylase activity and secretion of [14C]5-HT and [3H]protein; the ratios of [3H]protein/[14C]5-HT in zymogen granules and in the secretory products are identical. Pancreas acinar cells take up L-DOPA, decarboxylate it and store the dopamine produced in zymogen granules but the dopamine is not retained by the granules (t1/2 approximately equal to 90 min) and dopamine secretion from cells exposed to caerulein could not be demonstrated. It is concluded that 5-HT is a normal component of rat pancreas acinar cell zymogen granule. The granular amine has a turnover rate similar to that of granular protein and is released when the cells are stimulated to secrete protein. All the 5-HT released from the cell originates in zymogen granules.

5-Hydroxytryptophan↗
PubMed1982

Vitamin D receptors in isolated rat parotid gland acinar cells.

Rat parotid gland was examined for the presence of 1 alpha, 25-dihydroxycholecalciferol receptors using sucrose density gradient ultracentrifugation techniques. [3H] DHCC bound specifically and with high affinity to a 3.2 S protein present in nuclear and cytosolic fractions of isolated parotid acinar cells. Values for the equilibrium dissociation constant and for the receptor concentration were determined to be approx. 0.1 nM, and 12 fmol/mg protein, respectively. In competitive inhibition experiments, the 3.2 S protein displayed 100-fold lower affinity for 25-hydroxycholecalciferol than for DHCC, and did not bind estradiol or methylprednisolone. These results suggest that rat parotid gland acinar cells contain classical DHCC receptors. A similar approach failed to provide evidence of DHCC receptors in isolated pancreas acinar cells, lacrimal gland or submandibular gland. It has been previously reported that vitamin D is essential for normal exocrine secretion from the rat parotid gland (Tenenhouse, A. and Afari, G. (1978) Biochim. Biophys. Acta 538, 631-634). The present findings suggest that this effect is the result of a direct action of DHCC on the parotid gland acinar cell. The absence of DHCC receptors in other exocrine cells suggests that tissue sensitivity to DHCC is not a general property of exocrine systems.

Animals↗
PubMed1982

The effects of theophylline and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724) on protein secretion from rat parotid gland.

1 The effects of two chemically distinct cyclic nucleotide phosphodiesterase (PDE) inhibitors on protein secretion from superfused rat parotid gland were studied.2 In the presence of 1.0 mM Ca(2+), Ro 20-1724 (10 muM), an imidazolidinone derivative, increased the secretory response to isoprenaline 100% and the isoprenaline-dependent accumulation of adenosine cyclic 3',5'-monophosphate (cyclic AMP) 300-400%. At this concentration Ro 20-1724 alone did not cause protein secretion, accumulation of cyclic AMP or significantly inhibit PDE activity in cell-free preparations from parotid gland.3 In the absence of added Ca(2+) and in the presence of 1.0 mM EGTA, Ro 20-1724 inhibited the secretory response to isoprenaline 65% while increasing isoprenaline-dependent cyclic AMP accumulation 200%.4 In the presence of Ca(2+), theophylline (10 mM) stimulated protein secretion but did not cause the accumulation of cyclic AMP. When combined with isoprenaline the rate of secretion was greater than the sum of the effects of the individual drugs but there was no effect of theophylline on the isoprenaline-dependent accumulation of cyclic AMP.5 Theophylline-stimulated protein secretion is increased by omitting Ca(2+) from the superfusion medium without any detectable change in cyclic AMP accumulation. Under these conditions Ro 20-1724 inhibits theophylline-stimulated protein secretion and the maximum rate of protein secretion in the presence of isoprenaline and theophylline is no greater than that seen with either agent alone.6 It is concluded that the theophylline effects do not result from inhibition of PDE. It is suggested that the primary action of both drugs on parotid gland acinar cells is to alter the distribution of intracellular Ca(2+). Ro 20-1724 may also inhibit Ca(2+)/calmodulin activated enzymes such as PDE.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1978

Protein secretion from parotid glands of vitamin D deficient and glucocorticoid-treated rats.

The rate of isoproterenol stimulated secretion of protein from parotid glands of vitamin D deficient rats and rats treated with methylprednisolone was increased compared to the secretory response of tissue from control rats. It is suggested that the increased secretory response is secondary to a decreased capacity of mitochondria from the tissue of these animals to take up and store Ca2+; i.e. the mitochondria are less efficient buffers of cytoplasmic Ca2+. Under these conditions any process, such as protein secretion, which requires an increased cytoplasmic Ca2+ concentration will operate more effectively.

Animals↗
PubMed1977

The effect of fasting on the in vitro synthesis of amylase in rat exocrine pancreas.

Immunological methods were used to study the effect of fasting on the in vitro synthesis of amylase (EC 3.2.1.1) in rat exocrine pancreas. After 72 h of fasting, the amylase enzyme activity of the pancreas and the rate of amylase synthesis were reduced 50%. No significant change in the activities of trypsin or chymotrypsin were detected. The decrease in leucine incorporation in total pancreas protein was accounted for by the decreased amylase synthesis. No change in the rate of amylase breakdown was detected. These results indicate that the rate of synthesis of amylase is controlled by food intake and is not directly related to the tissue content of enzyme.

Amylases↗
PubMed1976

The effect of dibutyryl cyclic adenosine-3'-5'-monophosphate on protein secretion from the rat exocrine pancreas in vitro.

1 The mechanism by which dibutyryl cyclic adenosine-3'-5'-monophosphate (dibutyryl cyclic AMP) potentiates the secretory effect of carbachol in rat exocrine pancreas was investigated. 2 Dibutyryl cyclic AMP potentiated the secretory effect of carbachol only at carbachol concentrations greater than or equal to 10(-7) mol/l; was independent of carbachol at concentrations greater than 10(-7) mol/l and was inversely proportional to extracellular [Ca2+]. 3 Carbachol increased and dibutyryl cyclic AMP reduced the rate of 45Ca efflux from the tissue. 4 A-23187 stimulated 3H-protein release in the presence of Ca2+ and this effect was potentiated by dibutyryl cyclic AMP; the degree of potentiation was inversely proportional to extracellular [Ca2+]. At 10(-3) mol/l [Ca2+] the potentiation occurred only at ionophore concentrations less than or equal to 10(-6) mol/litre. 5 These results support the hypothesis that dibutyryl cyclic AMP potentiates the effect of secretagogues in rat exocrine pancreas by maintaining an elevated intracellular calcium concentration. It does so by inhibiting Ca2+ efflux. The results also suggest that the limiting factor in carbachol-stimulated secretion, at all concentrations of carbachol, is intracellular [Ca2+].

Animals↗
PubMed1973

The relation of adenyl cyclase to the activity of other ATP utilizing enzymes and phosphodiesterase in preparations of rat brain; mechanism of stimulation of cyclic AMP accumulation by NaF.

1. A method for measuring the rate of production of (14)C-labelled adenine nucleotides, including cyclic adenosine 3',5'monophosphate (cyclic AMP), from [(14)C]-adenosinetriphosphate (ATP) was developed and used to study the effects of ATP, adenosine diphosphate (ADP) and adenosine 5'-monophosphate (AMP) on the rate of accumulation of cyclic AMP in cell-free preparations of adenyl cyclase from rat brain.2. The mechanism by which NaF increases cyclic AMP accumulation was studied by comparing its effect on adenine nucleotide metabolism with that of an ATP regenerating system.3. ADP and ATP are potent inhibitors of phosphodiesterase (PDE) and it is the sum of the concentrations of these two nucleotides which controlled the rate of destruction of cyclic AMP. The effect of these nucleotides was significant even in the presence of 6.7 mM theophylline; theophylline itself inhibited PDE only 50-60%.4. Fluoride ion had no direct effect on PDE but it inhibited the rate of hydrolysis of ADP and ATP and thus indirectly inhibited PDE. The effect of fluoride ion on cyclic AMP accumulation can be explained, at least in part, by this indirect inhibition of PDE.5. Studies on a more purified preparation of adenyl cyclase clearly demonstrated a direct action of NaF on adenyl cyclase.

Adenosine Diphosphate↗
PubMed1973

The relation of adenyl cyclase to the activity of other ATP utilizing enzymes and phosphodiesterase in preparations of rat brain; mechanism of stimulation of cyclic AMP accumulation by adrenaline, ouabain and Mn++.

1. The mechanism of stimulation of cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation by adrenaline and ouabain and the effect of Mn(++) substitution for Mg(++) as the metal ion requirement of this system was studied in cell-free preparations of adenyl cyclase from rat brain.2. In the rat cerebral cortex preparation, substitution of Mn(++) for Mg(++) significantly increased cyclic AMP accumulation while significantly inhibiting adenosine triphosphate (ATP) and adenosine diphosphate (ADP) hydrolysis and adenosine 5'-monophosphate (AMP) accumulation. In the synaptic membrane preparation, in the absence of NaF, the highest amount of ATP hydrolysis was obtained in tissue prepared with Mn(++) and incubated with Mg(++); under these conditions cyclic AMP accumulation was equal to that produced under any other condition and significantly higher than that observed in the presence of Mg(++) prepared and Mg(++) incubated tissue.3. Preparation and/or incubation of tissue with Mn(++) significantly reduced phosphodiesterase (PDE) activity compared to that observed in Mg(++) prepared tissue.4. Adrenaline and ouabain both significantly increased cyclic AMP accumulation in the rat cerebral cortex preparation but did not inhibit ATP or ADP hydrolysis. In the synaptic membrane preparation, in the presence of 0.01 mM Ca(++), adrenaline but not ouabain significantly increased cyclic AMP accumulation. Phenoxybenzamine (0.1 mM) and pronethalol (0.1 mM) significantly inhibited adrenaline-induced cyclic AMP accumulation in both these preparations.5. Ouabain and adrenaline both failed to stimulate cyclic AMP accumulation in the presence of Mn(++) prepared and/or incubated tissue.6. Ouabain and adrenaline had no effect on PDE activity in either of these preparations.7. It was concluded that Mn(++) increased cyclic AMP accumulation in part by indirect inhibition of ATP and ADP hydrolysis which provides inhibitors of cyclic AMP destruction, by direct stimulation of adenyl cyclase and by inhibition of cyclic AMP destruction in a way unrelated to nucleotide inhibition of PDE. Adrenaline and ouabain appeared tp stimulate cyclic AMP accumulation in a more direct manner.

Adenosine Diphosphate↗