Functional and Structural Adaptations in the Pancreatic alpha-Cell and Changes in Glucagon Signaling During Protein Malnutrition

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of non-steroidal anti-inflammatory drugs (NSAID) on the histamine release induced by compound 48/80 and cardiac anaphylaxis in guinea-pig isolated heart

Histamine release from guinea pig heart treated with compound 48/80 was potentiated by the cyclooxygenase inhibitors indomethacin and piroxicam but not by aspirin or phenylbutazone. This differential effect suggests that the potentiation is not merely due to an inhibition of prostaglandin synthesis. Piroxicam potentiated the histamine release induced by cardiac anaphylaxis whereas indomethacin reduced this effect. The SRS-A antagonist FPL 55712 inhibited histamine release induced by cardiac anaphylaxis, but not that evoked by compound 48/80, and also prevented the potentiation due to indomethacin and piroxicam. In total, these data suggest that the potentiation of histamine release by piroxicam and indomethacin is probably due to a diversion of arachidonic acid metabolism from the cyclooxygenase to the lipoxygenase pathways. The resulting lipoxygenase products may then regulate histamine release, with the secretion due to antigen being more sensitive to such modulation than that evoked by compound 48/80.

Influence of temperature on the release of plasminogen activator.

Fibrinolysis is a basic defense mechanism of the organism designed to control the deposition of fibrin in the vascular system and elsewhere. Fibrinolytic activity was measured by the fibrin plate method for three groups of rats (N = 6) that were maintained at room temperature, 20-25 degrees C, 3 degrees C or 38 degrees C for 4 h before testing. Based on measurement of fibrinolytic activity, the level of plasminogen activator released from isolated aortic segments of rats maintained at room temperature (24-28 degrees C) differed significantly from that of the 38 degrees C group. The animals maintained at 3 degrees C did not release plasminogen activator, suggesting that the fibrinolytic response was impaired at low temperature.

Agents that inhibit histamine release: A review

It is well known that histamine is found in high concentration in mast cell granules(1). The histamine content of these granules may be released to the extracellular space if an appropriate stimulus is provided(2). Besides histamine, other preformed active substances like enzymes, chemotatic factors and proteoglycans, as well as newly generated mediators like eicosanoids, platelet activating factor and adenosine are released during the secretion process of mast cells(3). The activation of mast cell degranulation has been associated with a number of pathologic disorders, most frequently, diseases derived from the atopic state(4). It is now evident that mast cells are the primary effector cells in the early reaction in both allergic and non-allergic asthma(5,6), although some authors doubt that the late reaction of asthma is a mast cell dependent event(6). Other studies point towards basophils as cellular elements involved in the secondary phase of inflammation in allergic diseases(7). Secretion would depend on a histamine releasing factor, and on the presence of IgE on the basophil's surface(8). There is also evidence suggesting involvement of mast cells in some non-allergic inflammatory processes like arthritis(9). The pharmacological management of these diseases basically consists in the use of methylxantines, beta 2-adrenergic agonists, glucocorticoids, sodium cromoglycate-like drugs, anticholinergic and antihistaminic H 1 antagonists(10). Their therapeutic effects include bronchodilatation, receptor and physiological antagonism, prevention of inflammatory responses induced by secondary cells, and finally, inhibition of mast cell activation(11). This review is concerned with compounds having inhibitory action on mast cell activation, and their possible importance on the pathophysiology of mast cell-related diseases.

The Effects of N Helix Deletion and Mutant F29W on the Ca2+ Binding and Functional Properties of Chicken Skeletal Muscle Troponin C

To assess the structural and functional significance of the N helix (residues 3-13) of avian recombinant troponin C (rTnC), we have constructed NHdel, in which residues 1-11 have been deleted, both in rTnC and in the spectral probe mutant F29W (Pearlstone, J. R., Borgford, T., Chandra, M., Oikawa, K., Kay, C. M., Herzberg, O., Moult, J., Herklotz, A., Reinach, F. C., and Smillie, L.B. (1992) Biochemistry 31, 6545-6553). Comparison of the far- and near-UV CD spectra (±Ca2+) of F29W and F29W/ NHdel and titration of the Ca2+-induced ellipticity and fluorescence changes indicates that the deletion has little effect on the global fold of the molecule but reduces the Ca2+ affinity of the N domain, but not the C domain, by 1.6-1.8-fold. Comparisons of the mutants NHdel, F29W, and F29W/NHdel with rTnC have been made using several functional assays. In reconstituted troponin-tropomyosin actomyosin subfragment 1 and myofibrillar ATPase systems, both F29W and NHdel have significantly reduced Ca2+-activated enzymic activities. These effects are cumulative in the double mutant F29W/ NHdel. On the other hand, maximal isometric tension development in Ca2+-activated reconstituted skinned fibers is not affected with F29W and NHdel, although the Ca2+ sensitivity of NHdel in this system is markedly reduced. We conclude that both mutations, NHdel and F29W, are functionally deleterious, possibly affecting interactions of the N domain with troponin I and/or T.

Histamine release induced by glucose (mannose)-specific lectins isolated from Brazilian beans. Comparison with concanavalin A

The histamine releasing properties of glucose (mannose)-specific lectins isolated from Brazilian beans was examined. The Canavalia brasiliensis, Dioclea rostrata, and Dioclea virgata lectins induced histamine release in rat peritoneal mast cells similar to concanavalin A. Less potency and efficacy was observed for Canavalia maritima, Dioclea guianensis, and Dioclea violacea while very low activities were seen for the lectins from Dioclea grandiflora, Canavalia bonariensis, and Cratylia floribunda. The histamine releasing effect was quenched by higher doses of D. virgata lectin similar to what was reported for concanavalin A. This effect was abrogated by increasing the concentration of calcium in the incubating medium. As these above proteins have sites that bind calcium, higher doses of the lectins might withdraw the calcium which is essential for the mast cell secretion.

Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia

The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 12 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 12 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1-2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration increased and haematocrit decreased during halothane anaesthesia. The concentrations of met-enkephalin, dynorphin and catecholamines did not change and those of β-endorphin, adrenocorticotrophin, arginine vasopressin and cortisol increased during halothane anaesthesia. Halothane appeared to be a major stimulus to pituitary adrenocortical activation because the adrenocortical secretion was proportional to the amount of halothane inhaled. β-endorphin increased proportionally more than adrenocorticotrophin and their plasma concentrations were not correlated, suggesting that they have independent secretion mechanisms.

Characteristics of the histamine release from hamster cheek pouch mast cells stimulated by lectins from Brazilian beans and concanavalin A

We have characterized the histamine releasing effects of lectins extracted from Brazilian beans, in comparison to concanavalin A, in hamster cheek pouch cell suspensions containing mast cells. The lectins from Dioclea virgata, Canavalia brasiliensis, and Dioclea rostrata induce histamine release in a similar manner to concanavalin A, but appear to differ in potency and efficacy. The effects depended on the temperature, pH, and metabolic energy, demonstrating the non-cytotoxic nature of the histamine release. It is suggested that the lectins studied act by the same mechanism as concanavalin A (interacting with sugars in the antibodies bound to the mast cells), since high concentrations of glucose inhibit the histamine release. The lectins at high concentrations quench the histamine release. This suppression is reversed by increasing calcium concentration, suggesting that the lectins bind to the calcium that is essential for the secretion, thereby confirming and extending our previous data using the lectin from Dioclea virgata in rat peritoneal mast cells.

Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake and release in rat striatal slices

Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic transmission through inhibition of dopamine uptake and enhanced release of the transmitter. We evaluated the changes in the inhibition of uptake and the release of striatal [ 3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200-250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were used. In the behavioral experiments the rats (N = 8 for each group) received FCF (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the duration of activity (sniffing, rearing and locomotion) was recorded for 120 min. The basal motor activity was higher (28.6 ± 4.2 vs 8.4 ± 3.5 s) after saline administration at 21:00 h than at 9:00 h. FCF at a single dose significantly enhanced the basal motor activity (38.3 ± 4.5 vs 8.4 ± 3.5 s) and increased the duration of exploratory activity (38.3 ± 4.5 vs 32.1 ± 4.6 s) during the light, but not the dark phase. Two other groups of rats (N = 6 for each group) were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine uptake and relase assays. The inhibition of uptake and release of [ 3H]-dopamine were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the release properties of FCF undergo daily variation. These data suggest that the circadian time-dependent effects of FCF might be related to a higher susceptibility of dopamine presynaptic terminals to the action of FCF during the light phase which corresponds to the rats' resting period.

Long-term effect of prolactin treatment on glucose-induced insulin secretion in cultured neonatal rat islets

Insulin secretion and 45SCa2+ uptake and efflux were studied in neonatal rat islets maintained in culture for 7 or 19 days in the absence or presence of prolactin (PRL). Insulin secretion in response to glucose (G), leucine (Leu), arginine (Arg) and carbachol (Cch) was augmented after 7 and 19 days in culture, compared to basal secretion (G 2.8 mM), in both PRL- treated and control islets. However, the increase in insulin secretion induced by the above secretagogues was higher in islets cultured in the presence of PRL for 19 days. In PRL-treated islets, the 45Ca2+ content after a 5 min incubation in the presence of G, Leu, Arg and Cch was significantly higher than the control only in islets cultured for 19 days. Except with Arg, the 45Ca2+ uptake in PRL-treated islets after a 90 min incubation was also significantly higher than the control only in islets cultured for 19 days. Finally, Leu-induced alterations in the 45Ca2+ efflux were higher in PRL-treated than in control islets cultured for 7 or 19 days. In the absence of external Ca2+, the reduction in 45Ca2+ efflux induced by glucose was also significantly higher in PRL-treated than in control islets. This effect was slightly potentiated after 19 days in culture. These data further support the hypothesis that PRL treatment enhances maturation of the secretory mechanism in neonatal islets. This effect can be potentiated even more if the treatment is prolonged.

Release of formaldehyde by 4 endodontic sealers

Objective. The purpose of this study was to evaluate the release of formaldehyde by some root canal filling materials. Study design. Two older endodontic sealers, AH 26 and Endomethasone, and 2 recently available sealers, AH Plus and Top Seal, were analyzed. Infrared and electronic spectroscopy were used to determine formaldehyde content after set of the materials. Results. Analysis showed that the AH 26 and Endomethasone sealers released formaldehyde. Although the AH Plus and Top Seal sealers have similar chemical composition, they released formaldehyde in a minimal concentration. Conclusions. The AH 26 and Endomethasone sealers released formaldehyde after setting; however, a minimum release was observed for the AH Plus and Top Seal sealers. Copyright © 1999 by Mosby, Inc.