Effect of PAF on parasympathetic contraction of canine airways

1989 ◽  
Vol 66 (6) ◽  
pp. 2629-2634 ◽  
Author(s):  
R. A. Bethel ◽  
S. P. Curtis ◽  
D. C. Lien ◽  
C. G. Irvin ◽  
G. S. Worthen ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Airway Hyperreactivity ◽  
Dependent Manner ◽  
Airway Edema ◽  
Potential Mediator ◽  
Lung Resistance ◽  
Trachealis Muscle ◽  
Dose Dependent

Platelet-activating factor (PAF) increases the bronchoconstrictor response of mammalian airways to cholinergic agonists and is thus implicated as a potential mediator of airway hyperreactivity. This study further defines the nature of the increase in airway responsiveness induced by PAF. We employed an in situ canine tracheal preparation, which allows differentiation of the effects PAF has on airway smooth muscle contraction from confounding effects it has on inducing airway edema and secretions. We found that PAF, infused regionally into tracheal arteries, increases the responsiveness of the trachealis muscle to parasympathetic stimuli in a dose-dependent manner. This effect occurred within 15 min. To determine whether the increase in trachealis muscle responsiveness resulted from effects localized to the trachea, we compared the effect of PAF on the tracheal segment with effects of the lower airways of the lung. Delivered to the arteries perfusing the tracheal segment, PAF did not increase lung resistance during vagus nerve stimulation. These data indicate that airway hyperresponsiveness elicited by PAF results from regional stimulation and/or release of mediators that augment tracheal contractility and that this effect is distinct from systemic effects elicited by PAF.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

PAF-induced contraction of canine trachea mediated by 5-hydroxytryptamine in vivo

1989 ◽  
Vol 66 (2) ◽  
pp. 638-643 ◽  
Author(s):  
T. M. Murphy ◽  
N. M. Munoz ◽  
J. Moss ◽  
J. S. Blake ◽  
M. M. Mack ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Contractile Response ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Active Tension ◽  
Response Curves ◽  
Arteriovenous Difference

We studied the secretory correlates of tracheal smooth muscle contraction caused by platelet-activating factor (PAF) in nine mongrel dogs in vivo. In five dogs, dose-response curves were generated by rapid intra-arterial injection of 10(-10) to 10(-6) mol PAF into the isolated tracheal circulation; tracheal contractile response was measured isometrically in situ. To examine the mechanism by which PAF elicits contraction of canine trachealis, concentrations of serotonin (5-HT) and histamine were assayed in the venous effluent as the arteriovenous difference (AVd) in mediator concentration across the airway for each level of contraction. PAF caused dose-related active tracheal tension to a maximum of 37.2 +/- 5.4 g/cm (10(-6) mol PAF). The AVd in 5-HT increased linearly from 0.20 +/- 0.05 (10(-9) mol PAF) to 3.5 +/- 0.3 ng/ml (10(-6) mol PAF) (P less than 0.005). In contrast, the AVd in histamine was insignificant and did not change with increasing doses of PAF. A positive correlation was obtained between the AVd in 5-HT and active tracheal tension (r = 0.92, P less than 0.001); there was no correlation between AVd in histamine and active tension (r = -0.16). PAF-induced parasympathetic activation was not mediated by 5-HT; contraction elicited by exogenous 5-HT was not affected by muscarinic blockade. We conclude that nonparasympathetically mediated contraction elicited acutely by PAF in dogs results at least in part from secondary release of serotonin and is not mediated by histamine.

Effects of cholecystokinin-octapeptide on gastric motility of anesthetized dogs

1986 ◽  
Vol 251 (5) ◽  
pp. G678-G681 ◽  
Author(s):  
A. Kuwahara ◽  
K. Ozawa ◽  
N. Yanaihara
Keyword(s):  
Smooth Muscle ◽  
Gastric Motility ◽  
Contractile Response ◽  
Smooth Muscle Contraction ◽  
Dependent Manner ◽  
Local Effects ◽  
Cholecystokinin Octapeptide ◽  
Gastric Smooth Muscle ◽  
Anesthetized Dogs ◽  
Dose Dependent

The present experiments examined the local effects of cholecystokinin-octapeptide (CCK-8) and related peptides on gastric motility of anesthetized dogs. Peptides were injected through the gastroepiploic artery at doses of 1.0, 2.5, 5.0, 10.0, and 20.0 ng/ml. CCK-8 and its analogues (Glt-CCK-8, pGlu-CCK-8, and Suc1-MePhe8-CCK-7) increased gastric smooth muscle contraction in a dose-dependent manner. ED50 of CCK-8 was 2.97 +/- 0.63 ng/ml. Administration of atropine (100–200 micrograms/kg) inhibited the effects of both CCK-8 and pentagastrin; however, hexamethonium (5 mg/kg) failed to block the contractile response induced by CCK-8 and pentagastrin. These results indicate that CCK-8 and related peptides can act as local modulators in controlling the neural regulation of gastric motility.

Determination of mosquito bloodmeal pH in situ by ion-selective microelectrode measurement: implications for the regulation of malarial gametogenesis

Parasitology ◽  
2000 ◽  
Vol 120 (6) ◽  
pp. 547-551 ◽  
Author(s):  
O. BILLKER ◽  
A. J. MILLER ◽  
R. E. SINDEN
Keyword(s):  
Xanthurenic Acid ◽  
Mosquito Vector ◽  
Dependent Manner ◽  
Ph Increase ◽  
Ph Range ◽  
Dose Dependent

Malarial gametocytes circulate in the peripheral blood of the vertebrate host as developmentally arrested intra-erythrocytic cells, which only resume development into gametes when ingested into the bloodmeal of the female mosquito vector. The ensuing development encompasses sexual reproduction and mediates parasite transmission to the insect. In vitro the induction of gametogenesis requires a drop in temperature and either a pH increase from physiological blood pH (ca pH 7·4) to about pH 8·0, or the presence of a gametocyte-activating factor recently identified as xanthurenic acid (XA). However, it is unclear whether either the pH increase or XA act as natural triggers in the mosquito bloodmeal. We here use pH-sensitive microelectrodes to determine bloodmeal pH in intact mosquitoes. Measurements taken in the first 30 min after ingestion, when malarial gametogenesis is induced in vivo, revealed small pH increases from 7·40 (mouse blood) to 7·52 in Aedes aegypti and to 7·58 in Anophěles stephensi. However, bloodmeal pH was clearly suboptimal if compared to values required to induce gametogenesis in vitro. Xanthurenic acid is shown to extend the pH-range of exflagellation in vitro in a dose-dependent manner to values that we have observed in the bloodmeal, suggesting that in vivo malarial gametogenesis could be further regulated by both these factors.

Characterization of the role of CaMKI-like kinase (CKLiK) in human granulocyte function

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 1076-1083 ◽  
Author(s):  
Sandra Verploegen ◽  
Laurien Ulfman ◽  
Hanneke W. M. van Deutekom ◽  
Corneli van Aalst ◽  
Henk Honing ◽  
...  
Keyword(s):  
Respiratory Burst ◽  
Critical Role ◽  
Neutrophil Migration ◽  
Platelet Activating Factor ◽  
Dependent Manner ◽  
Functional Responses ◽  
Effector Functions ◽  
C Terminus ◽  
Human Granulocytes ◽  
Dose Dependent

AbstractActivation of granulocyte effector functions, such as induction of the respiratory burst and migration, are regulated by a variety of relatively ill-defined signaling pathways. Recently, we identified a novel Ca2+/calmodulin-dependent kinase I-like kinase, CKLiK, which exhibits restricted mRNA expression to human granulocytes. Using a novel antibody generated against the C-terminus of CKLiK, CKLiK was detected in CD34+-derived neutrophils and eosinophils, as well as in mature peripheral blood granulocytes. Activation of human granulocytes by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF), but not the phorbol ester PMA (phorbol 12-myristate-13-acetate), resulted in induction of CKLiK activity, in parallel with a rise of intracellular Ca2+ [Ca2+]i. To study the functionality of CKLiK in human granulocytes, a cell-permeable CKLiK peptide inhibitor (CKLiK297-321) was generated which was able to inhibit kinase activity in a dose-dependent manner. The effect of this peptide was studied on specific granulocyte effector functions such as phagocytosis, respiratory burst, migration, and adhesion. Phagocytosis of Aspergillus fumigatus particles was reduced in the presence of CKLiK297-321 and fMLP-induced reactive oxygen species (ROS) production was potently inhibited by CKLiK297-321 in a dose-dependent manner. Furthermore, fMLP-induced neutrophil migration on albumin-coated surfaces was perturbed, as well as β2-integrin-mediated adhesion. These findings suggest a critical role for CKLiK in modulating chemoattractant-induced functional responses in human granulocytes.

scholarly journals In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

2020 ◽  
Author(s):  
Bo Liang ◽  
Xudong Yuan ◽  
Gang Wei ◽  
Wei Wang ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Povidone Iodine ◽  
Early Stage ◽  
Etiologic Agent ◽  
Dependent Manner ◽  
Forming Technology ◽  
Long Acting ◽  
Dose Dependent

AbstractTo curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

Epithelial modulation of preterm airway smooth muscle contraction

1993 ◽  
Vol 74 (3) ◽  
pp. 1437-1443 ◽  
Author(s):  
H. B. Panitch ◽  
M. R. Wolfson ◽  
T. H. Shaffer
Keyword(s):  
Mechanical Ventilation ◽  
Smooth Muscle ◽  
Preterm Infants ◽  
Airway Epithelium ◽  
Smooth Muscle Contraction ◽  
Airway Hyperreactivity ◽  
The Other ◽  
Maximal Response ◽  
Maximal Stress ◽  
Trachealis Muscle

To determine if epithelium from immature airways can modulate the responsiveness of smooth muscle, we studied paired trachealis muscle strips from preterm sheep. The epithelium was removed from one strip and left undisturbed in the other. Concentration-effect (CE) curves to acetylcholine (ACh), KCl, and isoproterenol were obtained. To evaluate maturational effects, responses to ACh and isoproterenol were studied in trachealis strips from adult airways. Maximal stress (Po) to ACh increased after epithelium removal in preterm (P < 0.05) but not adult strips. Epithelium removal caused a leftward shift of the ACh CE curves in both preterm and adult strips (P < 0.001) and a decrease in the dose required to achieve a one-half maximal response (ED50) in both preterm (P < 0.005) and adult strips (P < 0.05). The magnitude of the change in Po as well as in the ED50 for ACh between preterms and adults was similar. Epithelium removal did not alter either the Po or the CE curves of preterm strips stimulated by KCl. Response to isoproterenol in precontracted strips was enhanced in the presence of an intact epithelium in both groups (P < 0.05). These data demonstrate that preterm airway epithelium is able to modulate the responsiveness of smooth muscle. Additionally, the magnitude of the effect is unchanged with maturation. We speculate that damage of airway epithelium from mechanical ventilation may contribute to the increased incidence of airway hyperreactivity observed in preterm infants.

Effects of Platelet-Activating Factor on Leukocyte Adhesion in the Guinea Pig Aorta

1985 ◽  
Vol 43 ◽  
pp. 684-685
Author(s):  
Mary Kay Melden ◽  
Ronald G. Van Valen ◽  
Robert N. Saunders ◽  
Dean A. Handley
Keyword(s):  
Blood Vessel ◽  
Guinea Pig ◽  
Intravenous Injection ◽  
Leukocyte Adhesion ◽  
Platelet Activating Factor ◽  
Dependent Manner ◽  
Cardiac Effects ◽  
Small Vessels ◽  
Dose Dependent

Platelet-activating factor (PAF) is a potent mediator of immune anaphylaxis. In a dose-dependent manner, PAF can induce such effects as thrombocytopenia, neutropenia, hypotension, bronchoconstriction, hemoconcentration, and negative inotropic cardiac effects. By intradermal or intravenous injection, PAF has been shown to induce blood vessel hyperpermeability resulting in extravasation of plasma, leukocyte adhesion and subsequent diapedesis. However, most studies of endothelial-leukocyte interactions have been limited to small vessels. We have examined the effects of PAF on endothelial structure and leukocyte involvement in the guinea pig aorta.

Relationship between retinoic acid and sonic hedgehog, two polarizing signals in the chick wing bud

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3267-3274 ◽  
Author(s):  
J. Helms ◽  
C. Thaller ◽  
G. Eichele
Keyword(s):  
Retinoic Acid ◽  
Sonic Hedgehog ◽  
Positional Information ◽  
Limb Bud ◽  
Dependent Manner ◽  
All Trans Retinoic Acid ◽  
Wing Bud ◽  
Zone Of Polarizing Activity ◽  
Dose Dependent

Local application of all-trans-retinoic acid (RA) to the anterior margin of chick limb buds results in pattern duplications reminescent of those that develop after grafting cells from the zone of polarizing activity (ZPA). RA may act directly by conferring positional information to limb bud cells, or it may act indirectly by creating a polarizing region in the tissue distal to the RA source. Here we demonstrate that tissue distal to an RA-releasing bead acquires polarizing activity in a dose-dependent manner. Treatments with pharmacological (beads soaked in 330 micrograms/ml) and physiological (beads soaked in 10 micrograms/ml) doses of RA are equally capable of inducing digit pattern duplication. Additionally, both treatments induce sonic hedgehog (shh; also known as vertebrate hedgehog-1, vhh-1), a putative ZPA morphogen and Hoxd-11, a gene induced by the polarizing signal. However, tissue transplantation assays reveal that pharmacological, but not physiological, doses create a polarizing region. This differential response could be explained if physiological doses induced less shh than pharmacological doses. However, our in situ hybridization analyses demonstrate that both treatments result in similar amounts of mRNA encoding this candidate ZPA morphogen. We outline a model describing the apparently disparate effects of pharmacologic and physiological doses RA on limb bud tissue.

Effects of interleukin 5-induced pulmonary eosinophilia on airway reactivity in the guinea pig

1996 ◽  
Vol 270 (3) ◽  
pp. L368-L375 ◽  
Author(s):  
C. M. Lilly ◽  
R. W. Chapman ◽  
S. J. Sehring ◽  
P. J. Mauser ◽  
R. W. Egan ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Histological Grade ◽  
Platelet Activating Factor ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
Interleukin 5 ◽  
Dose Dependent

Administration of interleukin 5 (IL-5) to guinea pigs by tracheal injection was associated with increased recovery of eosinophils and neutrophils from bronchoalveolar lavage (BAL) fluid. The number of eosinophils recovered from BAL fluid increased in a dose-dependent manner from 9 +/- 2 X 10(3)/ml to a plateau of 143 +/- 29 X 10(3)/ml after the administration of recombinant human IL-5 (rhIL-5). Tracheal administration of recombinant guinea pig IL-5 (gpIL-5) also increased eosinophil recovery but was less potent than rhIL-5. Histological analysis confirmed the presence of inflammatory cells in the lung; there were higher grades of inflammation in airway than in parenchymal tissue after gpIL-5 administration. In addition, the histological grade of airway inflammation was greater 24 and 72 h after gpIL-5 administration than it was 6 days after administration. Airway hyperresponsiveness is reported to occur in guinea pigs exposed to rhIL-5 by intraperitoneal cellular production. It is surprising that airway infiltration with eosinophils induced by the topical application of IL-5 was not associated with hyperresponsiveness to substance P, histamine, or platelet-activating factor in intact animals or to methacholine in tracheally perfused lungs. Furthermore, the microvascular leakage induced by substance P was not altered by rhIL-5 administration. These findings indicate that the presence of eosinophils alone is not sufficient for the expression of airway hyperresponsiveness. Our ability to separate eosinophil recruitment and retention in the tissues from airway hyperresponsiveness indicates that these two processes are distinct and that the presence of eosinophils in lung tissue, by itself, is not sufficient to alter airway contractile responses.

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