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At least 937 records · Page 52Linked to original sources
PubMed1997

Sodium metabisulfite and citric acid induce bronchoconstriction via a sulfite-sensitive pathway in the isolated guinea pig lung.

Inhalation of sodium metabisulfite (MBS; 80 mM; pH 2.9 +/- 0.1) or citric acid (CA; 0.4 M; pH 2.0 +/- 0.1) aerosols induced a reduction in compliance and conductance in the isolated perfused and ventilated guinea pig lung without affecting perfusion flow. The effect was dependent on the pH of the nebulized solution since inhalation of 80 mM MBS aerosols at pH 7.4 did not induce any effect on bronchial tone. Concomitantly to the bronchoconstriction induced by MBS or CA an increased level of calcitonin gene-related peptide (CGRP-LI) in the effluent perfusate was observed, indicating activation of sensory nerves. Sodium sulfite, a dissolution product of MBS, has previously been shown by our studies to reduce bronchoconstriction induced by inhalation of sulfur dioxide, in the isolated perfused and ventilated guinea pig lung. In the present study perfusion of the lung with sodium sulfite (3 mM) before and during exposure to aerosols with either MBS or CA attenuated the bronchoconstriction induced by the acidic solutions. The release of CGRP-LI induced by MBS or CA was not affected by sodium sulfite. Sulfite treatment did not modify perfused guinea pig lung reactivity towards acetylcholine (4 nmol), bradykinin (100 pmol), histamine (10 nmol), serotonin (500 pmol) and substance P fragment 5-11, a substance P analogue resistant to degrading enzyme (500 pmol). However, an inhibitory effect by sodium sulfite was observed on bronchoconstriction induced by the NK-2 agonist neurokinin A fragment 4-10 (NKA 4-10, 25 pmol). These results indicate that MBS- or CA-induced bronchoconstriction was dependent on the low pH of the aerosol solution and coincided with activation of sensory nerves. Sulfite modulation of the bronchoconstricting action of inhaled MBS and CA is suggested to be related to a sulfite-sensitive step in the signal transduction of the neuropeptide NKA.

Acetylcholine↗
PubMed1984

Inhibition of slow-reacting substance release by calmodulin blocker.

It was examined whether a calmodulin blocker could inhibit release of slow-reacting substance from human leukocytes. W-7, a specific calmodulin blocker, completely inhibited slow-reacting substance release induced by calcium ionophore or mite allergen at 5 X 10(-5) M, while W-12, which had a lower affinity to calmodulin, failed to inhibit the release even at 10(-4) M. It was suggested that calmodulin was involved in mechanisms of slow-reacting substance release. Release of PGE2 and PGF2 alpha by calcium ionophore was partially inhibited by 5 X 10(-5) M of W-7. The inhibitory effects of W-7 on slow-reacting substance release could be considered responsible for the suppression of phospholipase A2.

Autacoids↗
PubMed1994

Histamine, tryptase, norepinephrine, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II in plasma of patients with hymenoptera venom anaphylaxis.

Markers of immediate-type hypersensitivity such as histamine and tryptase were measured in the plasma of nonallergic volunteers and patients with a history of hymenoptera venom anaphylaxis. No significant differences in histamine or tryptase were found between patients and controls. Norepinephrine, an important compound involved in the control of cardiovascular functions and blood pressure, was the same in patients and nonallergic volunteers. In addition, components of the renin-angiotensin system were determined. Patients with hymenoptera venom anaphylaxis showed significantly lower plasma angiotensinogen concentrations as compared to healthy nonallergic controls (p < 0.007), whereas plasma ACE activity was the same. Likewise, the plasma levels of angiotensin I and angiotensin II were significantly reduced in patients as compared to controls (p < 0.04 and p < 0.003, respectively). These findings suggest that the renin-angiotensin system may play an important role as a counteracting factor in hymenoptera venom anaphylaxis.

Adult↗
PubMed1996

KW-4679, an antiallergic drug, inhibits the production of inflammatory lipids in human polymorphonuclear leukocytes and guinea pig eosinophils.

The effects of (Z)-11-[(3-dimethylamino)propylidene]-6,11-dihydrodibenz [b.e.]oxepin-2-acetic acid monohydrochloride (KW-4679), an orally active antiallergic drug, on the production of platelet-activating factor (PAF), leukotriene (LT) and thromboxane (TX) induced by Ca2+ ionophore A23187 were examined. KW-4679 at 10 microM reduced the amount of cell-associated PAF by 52.8% in human polymorphonuclear leukocytes (PMNs). KW-4679 (1-100 microM) also inhibited the release of both LTB4 and TXB2, a stable metabolite of TXA2, by human PMNs in a concentration-dependent manner, but did not influence the release of beta-glucuronidase. The 50% inhibitory concentration (IC50) values for LTB4 and TXB2 release were 5.9 and 6.0 microM, respectively. In guinea pig eosinophils, KW-4679 inhibited the release of peptide LTs at a concentration higher than 10 microM (IC50 = 66.9 microM). KW-4679 failed to inhibit PAF acetyltransferase, 5-lipoxygenase and TX synthase, but inhibited the arachidonic acid release by human PMNs in a concentration-dependent manner in a similar concentration as that inhibiting production or release of lipid mediators (IC50 = 19.5 microM). These results indicate that KW-4679 suppresses LTs and TX release and PAF formation by reducing arachidonic acid release from phospholipids, probably through interference with phospholipase A2. The inhibitory action of KW-4679 on PAF, LT and TX production is a beneficial effect of an antiallergic drug.

Acetyltransferases↗
PubMed2001

Selective inhibition of the renal angiotensin type 2 receptor increases blood pressure in conscious rats.

The angiotensin II type 2 (AT(2)) receptor is present in rat kidney; however, its function is not well understood. The purpose of this study was to evaluate the role of the AT(2) receptor in blood pressure (BP) regulation. The effects of selective inhibition of the renal AT(2) receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) were examined in conscious uninephrectomized rats. Oligodeoxynucleotides (AS-ODN or scrambled [S-ODN]) were infused directly into the renal interstitial space by using an osmotic pump at 1 microL/h for 7 days. Texas red-labeled AS-ODN was distributed in renal tubules in the infused but not the contralateral kidney of normal rats. Continuous renal interstitial infusion of the AS-ODN, but not S-ODN, caused a significant (P<0.01) increase in BP 1 to 5 days after the initiation of the infusion. AS-ODN-treated rats experienced an increase in systolic BP from 109+/-4 to 130+/-4 mm Hg (n=8, P<0.01), whereas S-ODN-treated (n=8) and vehicle-treated (n=8) rats did not show any significant change in BP. On day 5 of the oligodeoxynucleotide infusion, AS-ODN-treated rats exhibited a greater pressor response to systemic angiotensin II infusion (30 ng/kg per hour) than did S-ODN-treated rats (P<0.01). Renal interstitial fluid cGMP decreased from 11.9+/-0.8 to 3.6+/-0.5 pmol/mL (P<0.001), and bradykinin decreased from 0.05+/-0.05 to 0.18+/-0.03 ng/mL (P<0.001) in response to AS-ODN, but they were not significantly changed in response to S-ODN. To evaluate the effects of AS-ODN and S-ODN on AT(2) receptor expression, Western Blot analysis was performed on treated kidneys. Kidneys treated with AS-ODN had approximately 40% less expression of AT(2) receptor than did kidneys treated with S-ODN or vehicle (P<0.05). These results suggest that AS-ODN directed selectively against the renal AT(2) receptor decreased receptor expression and caused an increase in BP. We conclude that the renal AT(2) receptor plays an important role in the regulation of BP via a bradykinin/cGMP vasodilator signaling cascade.

Actins↗
PubMed1988

Mediator release in an isolated airway segment in subjects with asthma.

To determine if mediator release would occur in the airways of human subjects after exposure to a hyperosmolar stimulus, we challenged isolated airway segments in vivo with 900 mosmol sodium chloride using a specially designed double-balloon catheter. In order to determine if differences in mediator concentrations correlated with airway responsiveness or with atopy, we studied 3 separate groups: 6 atopic, asthmatic subjects; 6 atopic, nonasthmatic subjects; and 6 nonatopic, nonasthmatic normal subjects. In addition, to determine if the presence of the catheter itself was a stimulus, we studied 6 atopic, asthmatic subjects after exposure to isotonic sodium chloride alone (sham exposure). Lavage specimens were assayed for PGD2, PGF2 alpha, PGE2, TxB2, LTC4, and LTB4 by radioimmunoassay and for histamine by the modified single isotope enzymatic assay. The histamine concentration of the baseline lavage samples (bronchoalveolar lavage and isolated airway segment lavage) for the subjects with asthma were significantly greater than for the atopic or normal subjects (p less than 0.05). There was a significant negative correlation between histamine concentration in the lavage samples and the airway responsiveness of the subjects (r = -0.53, p less than 0.0001). There was a marked correlation among the concentrations of histamine, PGD2, PGF2 alpha, and TxB2 in all the lavage fluids for the subjects with asthma (p less than 0.03 for all comparisons and p less than 0.0001 for overall concordance). As a result of hyperosmolar challenge, there was a significant increase in the concentration of histamine, PGD2, and PGF2 alpha in the subjects with asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Reversal of leukotriene D4- and leukotriene E4-induced airway constriction in the guinea pig.

Conscious Hartley guinea pigs were challenged with LTD4 or LTE4 aerosols. When dynamic compliance (Cdyn) decreased to 50% of its baseline value, the challenge aerosols were stopped and treatment aerosols of salbutamol, the LTD4/E4 antagonist LY171883 Na, atropine, or sodium chloride (control) were begun. After 5 min of continuous exposure to the treatment aerosol, each animal was killed and excised lung gas volume (ELGV) was measured. Salbutamol was equally effective in reversing LTD4- and LTE4-induced Cdyn changes. Aerosolized LY171883 Na was effective against both agonists, but was about threefold more potent against LTE4. In contrast, atropine was very effective in reversing LTD4-induced Cdyn changes, but produced minimal reversal when LTE4 was the challenge agent. Pulmonary gas trapping results supported these observations; ELGV values were closely correlated with 5-min Cdyn measurements for both LTD4 (r = -0.817) and LTE4 (r = -0.831). Thus, although LTD4 and LTE4 are though to act on the same or similar receptors, the pattern of pharmacologic reversal at comparable levels of airway obstruction differs for these two agonists.

Acetophenones↗
PubMed1990

Airway levels of mast cell-derived mediators in exercise-induced asthma.

In order to assess the role of mast cell-derived mediators in the pathogenesis of exercise-induced asthma (EIA), we completed pre- and postexercise bronchoalveolar lavage (BAL) in seven atopic subjects with EIA. The study subjects were defined as having EIA if they exhibited a greater than 15% decrease in FEV1 after completing 6 min of treadmill exercise. There were no significant differences between mean preexercise and mean postexercise mast cell-derived BAL histamine (186 +/- 67 versus 148 +/- 36 pg/ml), tryptase (4.5 +/- 2.0 versus 2.8 +/- 2.0 ng/ml), prostaglandin D2 (26 +/- 11 versus 32 +/- 25 pg/ml), or leukotriene C4 (less than 100 versus less than 100 pg/ml). In addition, mast cells present in BAL fluid after exercise contained similar amounts of cellular histamine compared with BAL mast cells obtained before exercise (preexercise BAL cellular histamine, 26.6 +/- 12.3 ng/10(6) BAL cells; postexercise BAL cellular histamine, 22.7 +/- 9.1 ng/10(6) BAL cells), indicating that depletion of preformed mast cell mediators are unlikely to account for the refractory period in EIA. This study suggests that the cellular pathogenesis of EIA (mast cell-independent) differs from current theories of the pathogenesis of extrinsic allergen-induced asthma (mast cell-dependent).

Adolescent↗