Comparison of cholinergic and histaminergic axons in the lateral geniculate complex of the macaque monkey.
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The cholinergic and histaminergic projections have important neuromodulatory functions in the ascending visual pathways, so we compared the pattern and mode of innervation of the two projections in the lateral geniculate complex (dorsal lateral geniculate nucleus and pregeniculate nucleus) of the macaque monkey. Brain tissue from macaques was immunoreacted by means of antibodies to choline acetyltransferase (ChAT) or to histamine and processed for light and electron microscopy. A dense plexus of thin, highly branched ChAT-immunoreactive axons laden with varicosities was found in all layers of the dLGN including the koniocellular laminae and in the pregeniculate nucleus. ChAT label was more dense in magnocellular layers 1 and 2 than in parvocellular layers 3-6 and relatively sparse in the interlaminar zones. Varicosities associated with the cholinergic axons had an average of three conventional asymmetric synapses per varicosity, and these appeared to contact dendrites of both thalamocortical cells and interneurons. Histamine-immunoreactive axons were distributed homogeneously throughout all laminar and interlaminar zones of the dLGN, but were denser in the pregeniculate nucleus than in the dLGN. Histaminergic axons branched infrequently and were typically larger in caliber than cholinergic axons. The overwhelming majority of varicosities were found en passant and rarely displayed conventional synapses, despite the abundance of synaptic vesicles, and were not associated preferentially with specific cellular structures. The innervation of the macaque dLGN complex by cholinergic and histaminergic systems is consistent with their proposed role in state dependent modulation of thalamic activity. The dense and highly synaptic innervation by cholinergic axons supports the proposal of additional involvement of these axons in functions related to eye movements. (+info)
Measuring breathlessness during histamine challenge: a simple standardized procedure in asthmatic patients.
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One of the problems in research on symptom perception during histamine challenge has been the difficulty in finding both a valid and practical parameter of the "perceptiveness" for bronchoconstriction in a subject. The purpose of this study was to validate whether the slope in the linear regression model between stimulus and sensation during histamine challenge is an appropriate index for the "perceptiveness" for bronchoconstriction by comparing it with the classical Stevens' law. One hundred and thirty-four asthmatic patients were included in the study and underwent a bronchial challenge with histamine. The relationship between the change in visual analogue scale (VAS) values and the change in forced expiratory volume in one second (FEV1) as percentage of baseline value was analysed by determining both the exponent n in deltaVAS=k x (%deltaFEV1)n and the slope alpha in deltaVAS=k + alpha(%deltaFEV1). The best-fitting line of both the exponential and the linear regression model were determined by the least-squares method in which the percentage explained variation (R2) was compared. The median value of R2 of the exponential regression line and the linear regression line was 0.76 and 0.83, respectively, and significantly different. The Spearman rank correlation coefficient between exponent n in the exponential model deltaVAS=k x (%deltaFEV1)n and the slope alpha in the linear regression model deltaVAS=k + alpha(%deltaFEV1) was 0.87 (95% confidence interval 0.83-0.91). On the basis of the results, it was concluded that the linear regression coefficient can be used as a valid expression to describe the "perceptiveness" of an asthmatic subject instead of Stevens' power function during histamine challenge. (+info)
Mast cells and gastric secretion in the rat.
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Gastric secretion of acid was measured in adult rats deprived of solid food for 48 hr. In control animals, values were obtained for the residual content of acid in the stomach, indicative of the rate of basal secretion, and for the quantities of acid secreted in 30 min following injections of histamine, pentagastrin, insulin and compound 48/80. The same measurements were made in groups of rats treated for 5 days with compound 48/80 (a regime which depleted the whole body of mast cells) and for 3 days with dexamethasone (which selectively depleted the gastric mucosa of mast cells). The content of residual acid was depressed to one third of the control value in the 48/80-treated rats, but the additional secretion due to histamine, pentagastrin or insulin was unaffected. A secretory response to a single injection of compound 48/80 could not be obtained in rats depleted of mast cells. In the dexamethasone-treated rats, the residual level of acid was increased to 1-5 times the control value, but the magnitudes of the responses to secretogogues were unchanged. It is concluded that basal secretion of acid into the stomach of the rat is stimulated by histamine derived from mast cells throughout the body, those of the gastric mucosa having no special significance in this respect. Mast cells are not involved in the mediation of the secretagogue actions of exogenous histamine, pentagastrin and insulin, but the present results do not preclude the participation of histamine from sources other than mast cells in the process of gastric secretion. (+info)
Role of tachykinin NK2-receptor activation in the allergen-induced late asthmatic reaction, airway hyperreactivity and airway inflammatory cell influx in conscious, unrestrained guinea-pigs.
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1. In a guinea-pig model of allergic asthma, we investigated the involvement of the tachykinin NK2 receptors in allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperreactivity (AHR) after these reactions and inflammatory cell influx in the airways, using the selective non-peptide NK2 receptor antagonist SR48968. 2. On two different occasions, separated by a 1 week interval, ovalbumin (OA)-sensitized guinea-pigs inhaled either vehicle (3 min) or SR48968 (100 nM, 3 min) at 30 min before as well as at 5.5 h after OA provocation (between the EAR and LAR) in a random crossover design. 3. SR48968 had no significant effect on the EAR, but significantly attenuated the LAR by 44.2+/-16.4% (P<0.05) compared to saline control. 4. The NK2 receptor antagonist did not affect the OA-induced AHR to histamine after the EAR at 5 h after OA challenge (3.59+/-0.59 fold increase in histamine reactivity vs 3.79+/-0.61 fold increase in the controls, NS), but significantly reduced the AHR after the LAR at 23 h after OA challenge (1.59+/-0.24 fold increase vs 1.93+/-0.15 fold increase, respectively, P<0.05). 5. Bronchoalveolar lavage studies performed at 25 h after the second OA provocation showed that SR48968 significantly inhibited the allergen-induced infiltration of neutrophils (P<0.05) and lymphocytes (P<0.01) in the airways. 6. These results indicate that NK2 receptor activation is importantly involved in the development of the allergen-induced late (but not early) asthmatic reaction and late (but not early) AHR to histamine, and that NK2 receptor-mediated infiltration of neutrophils and lymphocytes in the airways may contribute to these effects. (+info)
Effect of early transient adherent leukocytes on venular permeability and endothelial actin cytoskeleton.
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In a time course study of the development and recovery of venular leaks, it was shown that, after as early as 3 min of histamine application, venular leak formation was identified [Baldwin, A. L., and G. Thurston. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1528-H1537, 1995]. This was accompanied by changes in the endothelial actin cytoskeleton and the presence of adherent leukocytes. The venular leaks remained elevated for at least 30 min, whereas the adherent leukocytes were decreased by 20 min. The present study was performed to determine the role that 3 min (early), transient histamine-associated adherent leukocytes play in the formation of venular leaks and changes in the endothelial actin cytoskeleton. In anesthetized rats, the microvasculature of a mesenteric window was perfused with buffered saline or fucoidin. FITC-BSA or FITC-BSA and 10(-4) M histamine was added to the perfusate for the last 3 min. The vasculature was perfusion fixed, stained for filamentous actin, and viewed microscopically. Fucoidin pretreatment significantly reduced the number of early, transient histamine-associated adherent leukocytes (P < 0.01). The number of adherent leukocytes in leaky venules was significantly greater than that seen in nonleaky venules (P < 0.01); however, the reduction in the number of histamine-associated adherent leukocytes with fucoidin pretreatment had no significant effect on the number (P > 0.05) or area (P > 0.05) of FITC-BSA leaks or on the endothelial actin cytoskeleton. (+info)
Effects of selected endothelium-dependent vasodilators on fetoplacental vasculature: physiological implications.
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The endothelium-dependent vasodilators ACh, histamine, and bradykinin were studied in the isolated, perfused human placental cotyledon. Histamine caused a decrease in perfusion pressure that was attenuated by cimetidine. Bradykinin, at lower concentrations (10(-20) to 10(-14) M), produced a concentration-dependent decrease in perfusion pressure, whereas at higher concentrations it produced an increase in perfusion pressure. ACh was without any effect. The decrease in perfusion pressure observed with bradykinin was potentiated by captopril and was significantly attenuated in the presence of HOE-140, the B(2)-receptor antagonist, or by pretreatment with an inhibitor of nitric oxide synthase, but not by an inhibitor of cyclooxygenase. The decrease in perfusion pressure observed with bradykinin was potentiated by ANG I but not by ANG II. It is concluded that endothelium-dependent vasodilation can be demonstrated with histamine and bradykinin in the fetoplacental vessels, and at least for bradykinin, this is partly mediated by release of nitric oxide. The potentiation of the bradykinin response in the presence of ANG I may serve to buffer the vasoconstriction produced by ANG II in the fetoplacental circulation. (+info)
Pre- and postjunctional effects of inflammatory mediators in horse airways.
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In addition to their direct contractile effects, histamine (Hist), serotonin [5-hydroxytryptamine (5-HT)], and leukotriene (LT) D(4), in low concentrations, dramatically augment electrical field stimulation (EFS)-induced smooth muscle contractions in equine airways. To determine the mechanism of their action, we studied, in trachealis strips, the effect of these mediators on both cholinergically induced tension and the release of ACh from cholinergic nerves. All three mediators synergistically augmented the contraction of the trachealis that was due to release of endogenous ACh, i.e., EFS-induced contraction. These same mediators caused only a small but parallel shift of the ACh concentration-response curve. Comparison of the mediator effects on the responses to endogenous and exogenous ACh suggested a prejunctional effect. However, release of ACh was augmented only by Hist and 5-HT but not by LTD(4). Hist-induced contraction of trachealis was abolished by pyrilamine (H(1)-receptor antagonist) but not by ranitidine (H(2)-receptor antagonist), whereas thioperamide (H(3)-receptor antagonist) shifted the Hist response curve to the left. The augmenting effect of Hist on EFS-induced contraction was abolished by pyrilamine and unaffected by ranitidine or thioperamide. We conclude that inflammatory mediators can increase endogenous cholinergic responses of equine airways via both prejunctional and postjunctional mechanisms. LTD(4) acts solely on smooth muscle, whereas 5-HT and Hist additionally act on neuronal receptors to facilitate release of ACh. Excitatory effects of Hist, i.e., direct contractile effect, and augmentation of endogenous cholinergic response are both mediated via H(1) receptors, whereas the inhibitory H(3) receptors partially oppose the direct contractile effect of this mediator. (+info)
CD69 surface expression on human lung eosinophils after segmental allergen provocation.
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CD69 expression on eosinophils is observed in asthma and has been proposed as a marker of eosinophil activation. The role of allergens in the in vivo regulation of CD69 expression on eosinophils, however, remains incompletely understood. It was therefore investigated whether CD69 expression on eosinophils can be induced by allergen provocation in vivo. Ten allergic asthmatics were studied by segmental allergen provocation. Two segments of the right and left lung were challenged with allergen or saline. CD69 expression was determined by flow cytometry and concentrations of interleukins were analysed by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid. Expression of CD69 on BAL eosinophils in the segments lavaged 10 min following saline instillation (28.3+/-8.8 specific mean fluorescence (SMF)) was not significantly different to segments lavaged 10 min after allergen (80.2+/-21.8 SMF) and segments lavaged 18 h after saline challenge (87.2+/-23.3 SMF). However, CD69 expression on eosinophils increased significantly 18 h after allergen challenge (128.6+/-21.9 SMF, p<0.03) which was accompanied by elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations (114.9+/-42.9 pg x mL(-1), p<0.05). CD69 expression on eosinophils and GM-CSF concentrations correlated 18 h following allergen provocation (r = 0.7, p<0.025). These results suggest that in allergic asthma there is an allergen dependent, endobronchial upregulation of eosinophil activation as assessed by CD69 expression on eosinophils. (+info)