Endogenous AA metabolites and their possible role in tracheal smooth muscle tone in guinea pigs

1990 ◽  
Vol 69 (1) ◽  
pp. 26-32 ◽  
Author(s):  
K. Yamane ◽  
T. Kobayashi
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Contractile Response ◽  
Muscle Tone ◽  
Tracheal Smooth Muscle ◽  
Base Line ◽  
Active Tension ◽  
Lipoxygenase Pathway

The effects of endogenous arachidonic acid (AA) metabolites on inherent tone and histamine-induced constriction were studied in guinea pig tracheal smooth muscle. Inhibitors of either cyclooxygenase (indomethacin) or lipoxygenase (AA 861) significantly diminished the inherent tone of the muscle. Antagonists of prostaglandins (SC 19220) or leukotrienes (FPL 55712) also diminished the inherent tone, whereas an inhibitor of thromboxane synthase (OKY 046) had no significant effect. These results show that the metabolites of the lipoxygenase pathway as well as prostaglandins also participate in the maintenance of inherent tone. To reexamine the previously reported augmentation of histamine constriction induced by the inhibitors and the antagonists, we compared the active tension of the muscle measured from the maximum relaxed level as the base line to eliminate the fluctuation of inherent tone. Such comparison revealed that the inhibitors and the antagonists have no augmentative effect on either the maximum response to histamine or the concentration required to produce 50% of maximum active tension and that there is functional synergism between the exogenously added histamine and the endogenously produced AA metabolites. Therefore the zero active tension is useful as a base line to compare the contractile response of a drug-treated preparation with that of a nontreated preparation.

Effect of mode of activation of human eosinophils on tracheal smooth muscle contraction in guinea pigs

1993 ◽  
Vol 264 (5) ◽  
pp. L475-L481
Author(s):  
M. E. Strek ◽  
S. R. White ◽  
T. R. Hsiue ◽  
G. V. Kulp ◽  
F. S. Williams ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Human Peripheral Blood ◽  
Total Content ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Kinetic Assay ◽  
Lipoxygenase Pathway ◽  
Threshold Response

We studied the relationship between mode of activation of isolated human eosinophils and in situ responsiveness in isolated tracheal smooth muscle (TSM) of guinea pigs. Human peripheral blood eosinophils were activated with either 10(-7) M phorbol myristate acetate (PMA) or 10(-6) M formyl-methionyl-leucyl-phenylalanine (fMLP) + 5 micrograms/ml cytochalasin B (CYB), and activation was confirmed by measurement of eosinophil peroxidase (EPO) secretion by kinetic assay. EPO secretion was similar after activation with fMLP+CYB (10.2 +/- 3.2% of total eosinophil content) and PMA (10.0 +/- 2.8% of total content; P = NS). Topical application of 6 x 10(6) eosinophils/cm2 activated with fMLP+CYB to the TSM segment caused 0.51 +/- 0.14 g/cm active tension (AT) in five preparations (P < 0.03 vs. baseline); cells activated with PMA caused no contractile response (0.04 +/- 0.03 g/cm AT, P = NS vs. baseline). Both PMA- and fMLP+CYB-activated cells caused augmentation of muscarinic responsiveness of guinea pig trachealis. The dose of intravenous acetylcholine required to cause a threshold response (ED0.3) was -7.3 +/- 0.1 log mol/kg at baseline vs. -8.7 +/- 0.5 log mol/kg after treatment with fMLP+CYB-activated eosinophils (P = 0.05) and -6.9 +/- 0.1 log mol/kg at baseline vs. -7.5 +/- 0.1 log mol/kg after PMA-activated cells (P < 0.01). Both AT and augmented muscarinic responsiveness were blocked by pretreating the eosinophils with 200 microM A-63162, an inhibitor of 5-lipoxygenase, before activation with fMLP+CYB. We demonstrate that eosinophils activated comparably (as assessed by EPO secretion) cause augmented muscarinic responsiveness and/or direct contraction of guinea pig TSM through secretion of a product of the 5-lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Desmodium adscendens fractions on antigen- and arachidonic acid-induced contractions of guinea pig airways

1988 ◽  
Vol 66 (6) ◽  
pp. 820-825 ◽  
Author(s):  
Marian E. Addy ◽  
John F. Burka
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Contraction ◽  
Aqueous Extract ◽  
Contractile Response ◽  
Late Phase ◽  
Smooth Muscle Contraction ◽  
Pharmacologically Active ◽  
Active Substances

Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.

scholarly journals Phenylethylamine effects on histamine-induced contraction of isolated guinea-pig trachea rings

2005 ◽  
Vol 24 (2) ◽  
pp. 95-97
Author(s):  
Gvozden Rosic ◽  
Zorica Lazic ◽  
Suzana Pantovic ◽  
Mirko Rosic
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Tone ◽  
Tracheal Smooth Muscle ◽  
Competitive Antagonist ◽  
Methyl Transferase ◽  
Basal Tone ◽  
H3 Receptors ◽  
Isolated Trachea ◽  
Histamine Methylation

Histamine produces constriction of tracheal smooth muscle via H1 receptors, but it also decreases tracheal smooth muscle tone via H2 and H3 receptors. In addition, it has already been reported that phenylethylamine is competitive antagonist of histamine N-methyl-transferase (HMT), enzyme responsible for rapid inactivation of histamine. Our results suggest possibility that phenylethylamine as competitive antagonist of histamine N-methyl-transferase leads to potentiation of histamine induced constriction of isolated guinea-pig trachea, which could be consequence of decreased histamine methylation and subsequent histamine inactivation. At the same time, phenylethylamine had no direct effect on basal tone of intact isolated trachea rings, as well as on other mechanisms leading to increased responsiveness of guinea-pig tracheal smooth muscle (acetylcholine, KCl, electro stimulation).

Effect of in vitro preconditioning on tracheal smooth muscle responsiveness

1991 ◽  
Vol 260 (2) ◽  
pp. L168-L173 ◽  
Author(s):  
R. W. Mitchell ◽  
E. Kelly ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Tissue Perfusion ◽  
Tracheal Smooth Muscle ◽  
Equilibration Time ◽  
Active Tension ◽  
Perfusion Chamber ◽  
Anesthetized Dogs

We evaluated the effect of preconditioning of the isometric contractile response of canine tracheal smooth muscle (TSM) in vitro. Strips of epithelium-free TSM (n = 90) were excised from 16 anesthetized dogs and fixed isometrically in tissue perfusion chambers. Experiments were performed using methods previously reported in which the following parameters were investigated: 1) quiescent equilibration time in the perfusion chamber (0-120 min); 2) effect of repeated exchange of perfusate; 3) method of determining the optimal resting length (Lmax) for presetting of resting tension (RT); 4) effect of precontraction during the equilibration phase on the contractile response to agonists administered subsequently; and 5) method of determining RT on the response to muscarinic stimulation. When other variables were uniform, neither equilibration time nor perfusate exchange affected potency or efficacy of the response generated subsequently to acetylcholine (ACh). However, both potency (range of EC50: -5.71 +/- 0.14 log M to -6.52 +/- 0.24 log M; P less than 0.02) and efficacy (range of maximal active tension: 1,143 +/- 268 g/cm2 to 2,878 +/- 151 g/cm2; P less than 0.001) of ACh were altered substantially as a result of the method used to estimate Lmax. Repeated precontraction by electrical field stimulation or with 127 mM KCl did not alter potency or efficacy of contraction elicited by ACh. Maximal active tension generated with 10(3) M ACh was 2,878 +/- 151 g/cm2 after 12–15 tetanizing field stimulations and 2,696 +/- 198 g/cm2 after 5–7 contractions with 127 mM KCl (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

K transport and mechanical responses of isolated longitudinal smooth muscle from guinea pig ileum

1961 ◽  
Vol 200 (4) ◽  
pp. 789-793 ◽  
Author(s):  
George B. Weiss ◽  
Robert E. Coalson ◽  
Leon Hurwitz
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Contractile Response ◽  
Muscle Tone ◽  
Muscle Layer ◽  
Smooth Muscle Contraction ◽  
Potassium Ion ◽  
Guinea Pig Ileum ◽  
Potassium Efflux ◽  
Longitudinal Smooth Muscle

The longitudinal smooth muscle layer of the guinea pig ileum was isolated in order to investigate its contractile responses and unidirectional K42 fluxes. Pilocarpine (7.5 x 10–6 m), acetylcholine (6.6 x 10–6 m), and a modified Tyrode's solution in which potassium ion was substituted for almost all the sodium ion were employed as excitatory agents. Cocaine (8.5 x 10–4 m) and a calcium-free Tyrode's solution served as inhibitory agents. Smooth muscle tone and potassium efflux of this relatively pure tissue were both increased by all three excitatory substances. Moreover, acetylcholine and pilocarpine produced a decrease in the influx of potassium ion. Bathing the tissue in a calcium-free medium for 1 hour before introducing pilocarpine to the muscle bath eliminated the contractile response that this drug ordinarily produces, but did not diminish appreciably the increase in K42 efflux. These observations are qualitatively similar to results previously obtained in analogous experiments on isolated whole ileum. In addition, cocaine (8.5 x 10–4 m) was found to block the contractile response and about three-quarters of the enhanced K42 efflux elicited by the isotonic potassium solution. It is presumed that cocaine acting at the membrane impedes ion fluxes important for smooth muscle contraction.

Mechanism of action of platelet-activating factor on guinea-pig lung parenchyma strips

1988 ◽  
Vol 66 (9) ◽  
pp. 1187-1191 ◽  
Author(s):  
Sonia Jancar ◽  
Patrick Thériault ◽  
Brigitte Provençal ◽  
Solange Cloutier ◽  
Pierre Sirois
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Acid Metabolism ◽  
Contractile Response ◽  
Platelet Activating Factor ◽  
Lung Parenchyma ◽  
Arachidonic Acid Metabolism ◽  
Lipoxygenase Inhibitor ◽  
Lipoxygenase Pathway ◽  
Thromboxane Synthetase

The contribution of thromboxane A2 to platelet-activating factor (PAF)induced contraction of guinea-pig lung parenchyma strips (GPLPS) was investigated using an experimental design that allowed us to record the contractions of the tissues in parallel with the determination of thromboxane B2 (TXB2) levels in the organ baths by enzyme immunoassay. It was found that the first injection of PAF induced the contraction of GPLPS and the release of TXB2. Following subsequent additions of PAF to the same tissue, the contractile response was abolished but TXB2 levels were not significantly reduced. Pretreatment of the tissue with the thromboxane synthetase inhibitor OKY-046 (3.5, 170, and 350 μM) strongly inhibited the release of TXB2 but had no effect on the contraction of the tissues induced by PAF. The mechanism of PAF-induced contraction of GPLPS was further investigated using several drugs that interfere with arachidonic acid metabolism. It was found that pretreatment of the tissues with the cyclooxygenase and thromboxane synthetase inhibitors indomethacin (2.8, 28, and 56 μM) and OKY-046 (170 μM) or with the thromboxane antagonist SKF-88046 (1.25 and 12.5 μM) had no significant effect on the contractile response to PAF. The compound L-655,240 (2.5, 25, and 50 μM), which acts simultaneously as an antagonist of thromboxane and inhibitor of lipoxygenase, significantly reduced GPLPS contractions induced by PAF. Another lipoxygenase inhibitor, nordihydroguaiaretic acid (33 μM), and the inhibitor of both pathways of arachidonic acid metabolism, BW775c (110 μM), both reduced PAF-induced contractions of GPLPS. We conclude that although PAF induces release of thromboxane from GPLPS, this mediator does not contribute significantly to the myotropic activity of PAF, which seems to be mediated by products of the lipoxygenase pathway.

Maturation of contractile response of ductus arteriosus to oxygen and drugs

1976 ◽  
Vol 231 (1) ◽  
pp. 240-243 ◽  
Author(s):  
S Noel ◽  
S Cassin
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Guinea Pig ◽  
Gestational Age ◽  
Guinea Pigs ◽  
Contractile Response ◽  
Ductus Arteriosus ◽  
Maximal Response ◽  
Contractile Responses ◽  
Oxygen Tensions

Contractile responses of rings of ductus arteriosus from fetal and neonatal guinea pigs were studied in buffered Krebs-Henseleit solutions of various oxygen tensions. Oxygen-induced contraction of ductus arteriosus increased with gestational age, peaking at term and attenuating within 24 h after birth. Contractions of ductus in response to potassium were not different in term and preterm fetuses. Maximal contractile response of pre- and postductal aortic rings to oxygen was 8.3% of the maximal oxygen-induced contraction of ductal rings from the same fetuses. Pulmonary artery was quite insensitive to oxygen. Of 12 ductus exposed to bradykinin in the absence of oxygen seven contracted (maximal response was obtained with 15.0 ng/ml). Exposure of ductus to bradykinin in the absence of oxygen enhanced subsequent contractions of ductal smooth muscle rings to air. Atropine failed to inhibit the oxygen-induced contraction of ductus. These data suggest that acetylcholine is not essential for oxygen-induced contraction of the guinea pig ductus arteriosus.

Noncholinergic contractile response to nicotine in the guinea pig isolated tracheal smooth muscle

1987 ◽  
Vol 65 (2) ◽  
pp. 269-271 ◽  
Author(s):  
Yasuo Kizawa ◽  
Issei Takayanagi
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Guinea Pig ◽  
Contractile Response ◽  
Tracheal Smooth Muscle ◽  
Muscle Preparation ◽  
Smooth Muscle Preparation ◽  
Substance P Antagonist

The existence of substance P immunoreactive nerves in the trachea of guinea pig is known. In this study, capsaicin induced a long-lasting and marked contraction in the guinea pig trachea and nicotine-induced contraction was partially reduced in the capsaicin-treated muscle. Furthermore, the contractile response to nicotine (10−5 M) in the presence of atropine (10−7 M) was abolished by a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]substance P (10−5 M). These findings suggest that noncholinergic contractile response to nicotine may be due to the release of material(s) resembling substance P in the isolated tracheal smooth muscle preparation of guinea pig.

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