Levamisole inhibits mineral mobilisation,lactate production and lysosomal enzyme release from cultured bones

Summary Levamisole added to cultured calvarial bones inhibited spontaneous bone resorption, as indicated by reduced release of calcium and inorganic phosphate to the medium. In addition, levamisole reduced lactate production and release of lysosomal enzymes.     

Peroxovanadate inhibits Ca2+ release from mitochondria

Mitochondria contain a specific Ca²⁺ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolyzed. NAD⁺ hydrolysis and therefore Ca²⁺ release is possible when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxovanadate inhibits the specific Ca²⁺ release pathway. In mitochondria, peroxovanadate causes a complete loss of reduced glutathione, which is not accompanied by formation of glutathione disulfide, and a partial loss of protein thiols. In model reactions, peroxovanadate oxidizes reduced glutathione predominantly to the sulfonate derivative, but does not react with glutathione disulfide. When the vicinal thiols relevant for Ca²⁺ release are cross-linked, Ca²⁺ release is no longer inhibited by peroxovanadate. Conversely, pretreatment of mitochondria with peroxovanadate makes them insensitive to compounds promoting the disulfide state. These results suggest that peroxovanadate inhibits the prooxidant-induced Ca²⁺ release from mitochondria by (i) depleting mitochondria of reduced glutathione and (ii) oxidizing the vicinal thiols relevant for Ca²⁺ release to a state higher than disulfide, presumably the sulfonate state. The findings provide further insight into the regulation of Ca²⁺ release from intact mitochondria, and may be relevant for a better understanding of the action of peroxovanadate in cells, where the compound can be insulin mimetic. Received 28 March 2002; received after revision 8 May 2002; accepted 15 May 2002     

Allergic reactions, cyclic AMP and histamine release.

Both isobutylmethylxanthine and theophylline increased the level cyclic AMP in the mast cell. Theophylline reduced the allergic histamine release, whereas isobutylmethylxynthine caused a pronounced potentiation of the histamine release. This indicates that the hypothesis of an inverse relationship between the level of cyclic AMP in mast cells and histamine release is too simple.     

Allergic reactions,cyclic AMP and histamine release

Summary Both isobutylmethylxantine and theophylline increased the level of cyclic AMP in the mast cell. Theophylline reduced the allergic histamine release, whereas isobutylmethylxynthine caused a pronounced potentiation of the histamine release. This indicates that the hypothesis of an inverse relationship between the level of cyclic AMP in mast cells and histamine release is too simple.This work was supported by grants from the Danish Medical Research Council (Grant No. 512-5270) and from Lundbeckfonden.     

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.     

Moderate cooling depresses the accumulation and the release of newly synthesized catecholamines in isolated canine saphenous veins

Moderate cooling (from 37 degrees to 24 degrees C) depressed the formation of 3H-dopamine and 3H-norepinephrine from 3H-tyrosine by isolated canine saphenous veins. Cooling reduced the evoked release of newly synthesized catecholamine to the same extent as that of stored norepinephrine. Hence the augmentation by cold of the contractile response to sympathetic nerve stimulation observed in earlier work is not accompanied by an augmented release of newly synthesized norepinephrine.     

Influence of somatostatin on serum prolactin concentrations of cows during rest and milking

Administration of somatostatin (SRIF) to lactating cows significantly increased basal, premilking serum concentrations of prolactin (PRL), and potentiated PRL release in response to milking and significantly reduced resting concentrations of growth hormone (GH).     

Inhibitory effect of atropine on the isoprenaline-induced increase in vasopressin plasma concentration in rats

The isoprenaline-induced increase in plasma levels of vasopressin in conscious rats was reduced by intravenous and intracerebroventricular applications of atropine. It is concluded that central neurons with muscarinic receptors contribute to the isoprenaline-induced vasopressin release.     

Inhibitory effect of atropine on the isoprenaline-induced increase in vasopressin plasma concentration in rats

Summary The isoprenaline-induced increase in plasma levels of vasopressin in conscious rats was reduced by intravenous and intracerebroventricular applications of atropine. It is concluded that central neurons with muscarinic receptors contribute to the isoprenaline-induced vasopressin release.     

The bisphosphonates HEBP and AHPrBP but not AHBP inhibit mineral mobilization and lysosomal enzyme release from mouse calvarial bones in tissue culture

The effect of 3 bisphosphonates, 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP), 3-amino-1-hydroxy-propylidene-1, 1-bisphosphonate (AHPrBP) and azacycloheptylidene-2, 2-bisphosphonate (AHBP), on the release of minerals (40Ca, 45Ca, Pi) and enzymes from cultured mouse calvaria was investigated in an organ culture system. HEBP and AHPrBP reduced PTH-stimulated mobilization of calcium and inorganic phosphate without affecting the release of lactate dehydrogenase. In contrast, no significant effect by AHBP on mineral mobilization and lysosomal enzyme release could be registered. In parallel with inhibited mineral mobilization, HEBP and AHPrBP inhibited the release of the lysosomal enzyme beta-glucuronidase. A possible cellular mechanism of action of bisphosphonates is discussed in the light of these data.     

The role of the autonomic nervous system in mediating pancreatic endocrine responses to arginine in the calf

The release of insulin which occurred in response to arginine, in the conscious calf, differed from that which occurs in response to glucose in that it was not significantly affected by either adrenergic or muscarinic blocking agents. Release of pancreatic glucagon was reduced by pretreatment with phentolamine.     

Influence of somatostatin on serum prolactin concentrations of cows during rest and milking

Summary Administration of somatostatin (SRIF) to lactating cows significantly increased basal, premilking serum concentrations of prolactin (PRL), and potentiated PRL release in response to milking and significantly reduced resting concentrations of growth hormone (GH).The author wishes to thank Ayerst Laboratories of Canada for donating the somatostatin for these studies.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats.

To study the effect of a sudden loss of body weight on the beta-cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Effects of 4-methyl-2-methylenevalerate,a non-metabolizable analogue of 2-ketoisocaproate,on insulin secretion and metabolism inob/ob mouse pancreatic islets

Summary To determine the importance of 2-ketoisocaproate metabolism in its insulin secretory action, 4-methyl-2-methylenevalerate, a non-metabolizable analogue, was tested for its ability to promote insulin secretion, and to interfere with the metabolism and insulin secretory action of 2-ketoisocaproate. 4-Methyl-2-methylenevalerate did not induce insulin release by isolatedob/ob mouse pancreatic islets, but it inhibited insulin release in response to 2-ketoisocaproate and reduced the rate of decarboxylation and oxidation of labeled 2-ketoisocaproate. The results suggest that 4-methyl-2-methylenevalerate interferes with the insulin secretory action of 2-ketoisocaproate, owing to their common brached-chain chemical structure.The skilful technical assistance of Miss S. Detels is gratefully acknowledged.     

Microclimatic origin of inhaled air affects olfactory navigation of homing pigeons

Earlier experiments led to the conclusion that homing pigeons are able to deduce positional information from atmospheric odours they perceive at the site of release. Here we show that this ability is significantly reduced, if the inhaled air does not originate from the free airspace in an open landscape but from a close-to-the-ground level of a forest or a maize field.     

A sperm GPI-anchored protein elicits sperm-cumulus cross-talk leading to the acrosome reaction

The acrosome reaction has long been thought to be induced by the zona pellucida. Here we report the identification and function of a novel human sperm glycosylphosphatidylinositol (GPI)-anchored membrane protein, NYD-SP8. The release of the protein during sperm-egg interaction and its binding to the cumulus, the first layer of egg investment, elicits cross-talk between the gametes and produces calcium dependant release of progesterone, which lead to the acrosome reaction. An in vivo mouse model of NYD-SP8 immunization is also established showing a reduced fertility rate. Thus, contrary to accepted dogma, our study demonstrates for the first time that, prior to reaching the zona pellucida, sperm may release a surface protein that acts on the cumulus cells leading to the acrosome reaction, which may be important for determining the outcome of fertilization. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Received 11 August 2008; received after revision 18 December 2008; accepted 22 December 2008     

Increased responsiveness of the hypothalamic-pituitary axis to steroid feedback effects in ovariectomized rats treated neonatally with monosodium L-glutamate

Summary Chronic ovariectomized rats treated neonatally with MSG showed reduced circulating concentrations of LH coupled with elevated hypothalamic LHRH stores. Despite the apparent loss of LHRH secretion, the small pituitary glands showed an increased density of LHRH receptors and normal responsiveness to the releasing hormone. The positive feedback effects of progesterone on LH release in oestrogen-primed animals was greatly exaggerated reflecting the build-up of hypothalamic LHRH stores without loss of pituitary responsiveness to LHRH.     

Increased responsiveness of the hypothalamic-pituitary axis to steroid feedback effects in ovariectomized rats treated neonatally with monosodium L-glutamate

Chronic ovariectomized rats treated neonatally with MSG showed reduced circulating concentrations of LH coupled with elevated hypothalamic LHRH stores. Despite the apparent loss of LHRH secretion, the small pituitary glands showed an increased density of LHRH receptors and normal responsiveness to the releasing hormone. The positive feedback effects of progesterone on LH release in oestrogen-primed animals was greatly exaggerated reflecting the build-up of hypothalamic LHRH stores without loss of pituitary responsiveness to LHRH.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats

To study the effect of a sudden loss of body weight on the -cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Über den Einfluss von Desoxycorticosteron auf Kontraktur und Kaliumfreisetzung durch Acetylcholin an der innervierten und denervierten Skelettmuskulatur

Summary The release of potassium ions from striated muscle, and the changes in mechanical tension developed by the gastrocnemius muscle on intraarterial injection of ACh, were investigated by isolated perfusion of the hind limbs in cats. The reaction of the normal innervated and chronically denervated muscle in the same animal were compared before and during perfusion with 2·10^–4 M/l desoxycorticosterone glucoside (DCG). The following results were obtained: after perfusion with DCG no change in the spontaneous release of potassium ions occurred neither on the innervated nor on the denervated muscle. The potassium release following intra-arterial injections of various doses of ACh was significantly reduced on innervated and denervated muscle. On the denervated muscle there was also a considerable reduction of the height of contractures caused by ACh administration. The results make it probable that DCG acts by an inhibition of depolarisation in the same way asd-tubocurarine.