A limited rote for leukotrienes and platelet-activating factor in food protein induced jejunal smooth muscle contraction in sensitized rats

1991 ◽  
Vol 69 (12) ◽  
pp. 1841-1846 ◽  
Author(s):  
R. B. Scott ◽  
M. Maric
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Receptor Antagonist ◽  
Contractile Response ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Food Protein ◽  
Lipoxygenase Inhibitor ◽  
Leukotriene Receptor ◽  
Web 2086

To determine whether the release of newly formed mediators such as the peptidoleukotrienes and platelet-activating factor might modulate the food protein induced jejunal smooth muscle contraction observed in sensitized rats, Hooded–Lister rats were sensitized by injection of ovalbumin (10 μg i.p.) and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally (n = 9) and circularly (n = 9) oriented jejunal segments (mucosa intact) were examined in standard tissue baths in response to antigen, leukotrienes, and platelet-activating factor alone and in the presence of a specific leukotriene receptor antagonist (MK-571), a 5-lipoxygenase inhibitor (L651,392), and a platelet-activating factor receptor antagonist (WEB 2086). Although the responses of control and sensitized tissues to stretch and 10−4 M bethanechol were similar, only sensitized tissues contracted in response to antigen (1 mg/mL). MK-571 (10−5 M) reduced or significantly inhibited the contractile response of sensitized longitudinally and circularly oriented tissues to 10−7 M leukotrienes C4, D4, or E4, but neither L651,392 (10−4 M) nor MK-571 (10−5 M) significantly reduced the contractile response of sensitized tissues to antigen challenge. WEB 2086 (10−4 M) significantly (p < 0.01) reduced the contractile response of sensitized longitudinally and circularly oriented tissues to 10−7 M platelet-activating factor but did not significantly alter the response to antigen in longitudinally (45% of control, p = 0.14) or circularly (118% of control, ns) oriented jejunal smooth muscle. In this model leukotrienes and platelet-activating factor play an insignificant role in modulating food protein induced jejunal smooth muscle contraction in intestinal anaphylaxis.Key words: leukotrienes, platelet-activating factor, smooth muscle, anaphylaxis, food allergy.

α-Adrenoceptor agonists and the Ca2+-dependence of smooth muscle contraction: evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction?

1985 ◽  
Vol 68 (s10) ◽  
pp. 55s-63s ◽  
Author(s):  
John C. McGrath
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Continuous Spectrum ◽  
Contractile Response ◽  
Nitrilotriacetic Acid ◽  
Smooth Muscle Contraction ◽  
Receptor Type ◽  
Receptor Interaction ◽  
Initial Transient ◽  
Adrenoceptor Agonists

1. The effects of varying [Ca2+]o on the contraction of smooth muscle by different α-adrenoceptor agonists were examined on rat isolated anococcygeus muscle. Agonists were tested in the presence of various [Ca2+]o or ‘Ca2+-re-addition curves’ were constructed. In some experiments the [Ca2+]free was buffered with EGTA and nitrilotriacetic acid. The components of the response which were revealed were further analysed by using drugs which modify Ca2+ mobilization. 2. Three separate elements in the contractile response were identified: (i) an initial transient contraction, due to intracellular Ca2+ release could be isolated with [Ca2+]o between 1 nmol/l and 3 μmol/l (this could be obtained only with noradrenaline, phenylephrine and amidephrine); (ii) a nifedipine-sensitive response requiring [Ca2+]o of 3 μmol/l or more; (iii) a nifedipine-resistant response requiring [Ca2+]o of 100 μmol/l or more. Presumably (ii) and (iii) involve the entry of Ca2+o: they could be obtained with all agonists tested, including these above, methoxamine, indanidine and xylazine. 3. The results are discussed in relation to the possibility of distinct types of response and their relationship to subgroups of receptors or agonists. It is concluded that there is a continuous spectrum of activity across the agonist range and that this is likely to correlate with ‘efficacy’ at a single α1 receptor type.

Contraction of guinea pig ileal smooth muscle by acetyl glyceryl ether phosphorylcholine

1981 ◽  
Vol 241 (3) ◽  
pp. C130-C133 ◽  
Author(s):  
S. R. Findlay ◽  
L. M. Lichtenstein ◽  
D. J. Hanahan ◽  
R. N. Pinckard
Keyword(s):  
Biological Activity ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Contraction ◽  
Glyceryl Ether ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction

Acetyl glyceryl ether phosphorylcholine (AGEPC) is a chemical that has the biological activity of what was formerly termed platelet-activating factor. We report here that synthetic AGEPC induces the contraction of guinea pig ileal smooth muscle. Antagonists of histamine, acetylcholine, and slow-reacting substances (SRS) do not block AGEPC-induced contraction. These responses were long lasting, resistant to washing, and displayed complete agonist specific desensitization. Histamine- and SRS-induced contractions were unaffected by AGEPC. These studies show that AGEPC has the potential to produce a component of anaphylactically induced smooth muscle contraction.

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.

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.

Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro

1988 ◽  
Vol 65 (2) ◽  
pp. 914-920 ◽  
Author(s):  
K. J. Popovich ◽  
G. Sheldon ◽  
M. Mack ◽  
N. M. Munoz ◽  
P. Denberg ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Airway Epithelium ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Serotonin Antagonist

To elucidate mechanisms of platelet-activating factor (PAF)-induced contraction, we studied the effect of PAF on 203 canine tracheal smooth muscle (TSM) strips from 45 dogs in vitro in the presence and absence of platelets. PAF (10(-11) to 10(-7) M) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 x 10(5) platelets/microliter, PAF was an extremely potent contractile agonist (threshold 10(-11) M). This response was inhibited by the PAF antagonist, CV-3988 (10(-6) M), and reversed by the serotonin antagonist, methysergide (EC50 = 3.7 +/- 0.79 x 10(-9) M). Neither atropine nor chlorpheniramine (10(-9) to 10(-6) M) attenuated the response to PAF + platelets. In the presence of platelets, 10(-7) M PAF caused an increase in perfusate concentration of serotonin from 0.93 +/- 0.037 x 10(-8) to 1.7 +/- 0.046 x 10(-8) M (P less than 0.001). Tachyphylaxis, previously demonstrated to be irreversible, was shown to be a platelet-dependent phenomenon; contraction could be repeated in the same TSM after addition of fresh platelets. We demonstrate that PAF-induced contraction of canine TSM is caused by the release of cellular intermediates such as serotonin from platelets. We also demonstrate the site of PAF-induced tachyphylaxis in airway smooth muscle contraction.

Contribution of intracellular calcium to gallbladder smooth muscle contraction

1990 ◽  
Vol 259 (1) ◽  
pp. G1-G5 ◽  
Author(s):  
L. M. Renzetti ◽  
M. B. Wang ◽  
J. P. Ryan
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Ethylene Glycol ◽  
Muscle Contraction ◽  
Contractile Response ◽  
Smooth Muscle Contraction ◽  
Physiological Salt Solution ◽  
Tetraacetic Acid ◽  
Optimal Length ◽  
Ethanesulfonic Acid

Studies were performed to evaluate the contribution of intracellular Ca2+ to gallbladder smooth muscle contraction under acetylcholine (ACh) or potassium stimulation. Gallbladder smooth muscle strips from adult guinea pigs were placed in tissue baths containing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered physiological salt solution (PSS) and set to optimal length for contraction (Lo). The results were as follows, 1) A 20-min equilibration in zero Ca2(+)-0.1 mM ethylene glycol-bis( beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) PSS virtually abolished the response to potassium but not to ACh. 2) Substitution of strontium, an inhibitor of intracellular Ca2+ release, for Ca2+ significantly decreased the contractile response to ACh (3 X 10(-5), 10(-4), and 3 X 10(-4) M). Strontium had no effect on the response to 40 and 80 mM potassium. 3) Intracellular Ca2+ depletion significantly decreased gallbladder smooth muscle contraction to ACh (10(-4) M) but had no effect on the response to potassium (80 mM). 4) Ryanodine, a compound that inhibits Ca2+ storage by the sarcoplasmic reticulum, significantly decreased the contractile response to ACh (10(-4) M) but not to potassium (80 mM). These data support the observation that the use of intracellular Ca2+ by gallbladder smooth muscle for contraction is agonist dependent.

Ectopic expression of caveolin-1 restores physiological contractile response of aged colonic smooth muscle

2007 ◽  
Vol 293 (1) ◽  
pp. G240-G249 ◽  
Author(s):  
Sita Somara ◽  
Robert R. Gilmont ◽  
Jeffrery R. Martens ◽  
Khalil N. Bitar
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Contractile Response ◽  
Colonic Motility ◽  
Smooth Muscle Contraction ◽  
Membrane Microdomains ◽  
Aged Rats ◽  
Wild Type ◽  
Caveolin 1

Reduced colonic motility has been observed in aged rats with a parallel reduction in acetylcholine (ACh)-induced myosin light chain (MLC20) phosphorylation. MLC20 phosphorylation during smooth muscle contraction is maintained by a coordinated signal transduction cascade requiring both PKC-α and RhoA. Caveolae are membrane microdomains that permit rapid and efficient coordination of different signal transduction cascades leading to sustained smooth muscle contraction of the colon. Here, we show that normal physiological contraction can be reinstated in aged colonic smooth muscle cells (CSMCs) upon transfection with wild-type caveolin-1 through the activation of both the RhoA/Rho kinase and PKC pathways. Our data demonstrate that impaired contraction in aging is an outcome of altered membrane translocation of PKC-α and RhoA with a concomitant reduction in the association of these molecules with the caveolae-specific protein caveolin-1, resulting in a parallel decrease in the myosin phosphatase-targeting subunit (MYPT) and CPI-17 phosphorylation. Decreased MYPT and CPI-17 phosphorylation activates MLC phosphatase activity, resulting in MLC20 dephosphorylation, which may be responsible for decreased colonic motility in aged rats. Importantly, transfection of CSMCs from aged rats with wild-type yellow fluorescent protein-caveolin-1 cDNA restored translocation of RhoA and PKC-α and phosphorylation of MYPT, CPI-17, and MLC20, thereby restoring the contractile response to levels comparable with young adult rats. Thus, we propose that caveolin-1 gene transfer may represent a promising therapeutic treatment to correct the age-related decline in colonic smooth muscle motility.

Characterization of tachykinin receptors in ferret trachea by peptide agonists and nonpeptide antagonists

1993 ◽  
Vol 265 (2) ◽  
pp. L164-L169 ◽  
Author(s):  
P. Geppetti ◽  
C. Bertrand ◽  
E. Bacci ◽  
O. Huber ◽  
J. A. Nadel
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Receptor Antagonist ◽  
Smooth Muscle Contraction ◽  
Neurokinin A ◽  
Dependent Manner ◽  
Nk1 Receptor ◽  
Tachykinin Receptors ◽  
Selective Agonists

The tachykinin receptors mediating mucus secretion and smooth muscle contraction were studied in the ferret trachea in vitro. Substance P (SP) and the selective agonist for NK1 receptor ([Sar9,Met(O2)11]SP), but not selective agonists for NK2 ([Ala5,beta-Ala8]neurokinin A-(4–10)) and NK3 ([MePhe7]neurokinin B) receptors, induced secretion of macromolecules in a concentration-dependent fashion. The nonpeptide NK1 receptor antagonist, CP-96,345, but not the nonpeptide NK2 receptor antagonist, SR-48968, inhibited SP-induced secretion. Both neurokinin A (NKA) and [Ala5,beta-Ala8]NKA-(4-10), but not NK1 and NK3 selective agonists, evoked a concentration-dependent smooth muscle contraction. SR-48968, but not CP-96,345, inhibited in a concentration-dependent manner the response to NKA. CP-96,345 and SR-48968 did not affect the concentration-dependent increase in macromolecule secretion or smooth muscle contraction by carbachol. These findings indicate that NK1 receptors mediate secretion of macromolecules and NK2 receptors mediate smooth muscle contraction, in response to tachykinins in the ferret trachea in vitro.

The receptor antagonist picotamide inhibits adrenergic and thromboxane-induced contraction of hyperplastic human prostate smooth muscle

2013 ◽  
Vol 305 (10) ◽  
pp. F1383-F1390 ◽  
Author(s):  
Martin Hennenberg ◽  
Marijan Miljak ◽  
Daniel Herrmann ◽  
Frank Strittmatter ◽  
Sebastian Walther ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Receptor Antagonist ◽  
Smooth Muscle Actin ◽  
Specific Antigen ◽  
Smooth Muscle Contraction ◽  
Human Prostate ◽  
Adrenoceptor Agonist ◽  
Human Prostate Tissue ◽  
Epithelial Marker

Inhibition of prostate smooth muscle contraction is an important strategy for medical treatment of lower urinary tract symptoms (LUTS). Besides α1-adrenoceptors, prostate smooth muscle contraction is induced by activation of thromboxane (TXA2) receptors (TXA2-R). Here, we examined the effects of the TXA2-R antagonist picotamide on contraction of human prostate tissue. Prostate tissues were obtained from radical prostatectomy. The effects of picotamide (300 μM), L-665,240 (3 μM), and seratrodast (3 μM) on U46619-, electric field stimulation- (EFS-), phenylephrine-, and norepinephrine-induced contractions were studied in organ baths. Expression of TXA2-R and TXA2 synthase (TXS) was examined by fluorescence stainings. Picotamide, seratrodast, and L-655,240 inhibited concentration-dependent contractions induced by the TXA2 analog U46619. Picotamide, but not seratrodast or L-655,240, inhibited frequency-dependent contractions induced by EFS. Picotamide inhibited concentration-dependent contractions induced by norepinephrine or by the selective α1-adrenoceptor agonist phenylephrine. In prostate strips, where only submaximal contraction by a low dose of phenylephrine was induced, application of U46619 raised tone to maximum phenylephrine-induced tension. Immunoreactivity for TXA2-R and TXS was observed in the stroma and in epithelial cells of glands. Colocalization of both immunoreactivites was observed with the smooth muscle markers calponin and α-smooth muscle actin, with the epithelial marker pan-cytokeratin, and with prostate-specific antigen in the stroma and glands. The receptor antagonist picotamide inhibits α1-adrenergic, TXA2-mediated, and EFS-induced contractions in the human prostate. To the best of our knowledge, this is the first antagonist able to inhibit two different contraction systems in the prostate.

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