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Carol A Hirshman - One of the best experts on this subject based on the ideXlab platform.
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basenji greyhound dog increased m2 muscarinic receptor expression in Trachealis Muscle
American Journal of Physiology-lung Cellular and Molecular Physiology, 1995Co-Authors: C W Emala, A Aryana, Michael A Levine, Robert P Yasuda, S A Satkus, B B Wolfe, Carol A HirshmanAbstract:Airway smooth Muscle from asthmatic humans and from the Basenji-greyhound dog (BG) dog is hyporesponsive to beta-adrenergic agonist stimulation. Because adenylyl cyclase is under dual regulation in airway smooth Muscle, we compared muscarinic receptor-coupled inhibition of adenylyl cyclase in airway smooth Muscle from BG and mongrel dogs. Inhibition of forskolin-stimulated adenylyl cyclase activity by the muscarinic M2 agonist oxotremorine was greater in airway smooth Muscle membranes from BG compared with mongrel controls. Quantitative immunoprecipitation studies showed increased numbers of m2 but not m3 muscarinic receptors in the BG airway smooth Muscle. The enhanced ability of muscarinic agonists to inhibit adenylyl cyclase in BG airway smooth Muscle may be due to the greater numbers of muscarinic m2 receptors, which may account in part for impaired airway smooth Muscle relaxation in the BG model of airway hyperresponsiveness.
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interaction between halothane and the nonadrenergic noncholinergic inhibitory system in porcine Trachealis Muscle
Anesthesiology, 1994Co-Authors: Karen S Lindeman, Stuart G Baker, Carol A HirshmanAbstract:BACKGROUND Volatile anesthetics significantly affect cholinergic neural transmission in the airways and relax airway smooth Muscle. Activation of the nonadrenergic, noncholinergic inhibitory neural pathway, which is thought to be mediated by nitric oxide, relaxes human and procine airways. The purpose of the current study was to determine in the isolated porcine Trachealis Muscle whether relaxation of airway smooth Muscle by halothane is mediated in part by activation of the nonadrenergic, noncholinergic inhibitory system. METHODS Isometric tension was measured in porcine Trachealis Muscle suspended in tissue baths in the presence of propranalol (10(-6) M). After stimulation of postsynaptic nicotinic cholinergic receptors with 1,1-dimethyl-4-phenyl-piper-azinium iodide (10(-4) M) to prevent contractile responses to subsequent electrical field stimulation, carbachol (3 x 10(-7) M) was added to increase tone. Nonadrenergic, noncholinergic relaxation responses to electrical field stimulation were then measured in the presence of inhibitors of nitric oxide synthase or L-arginine (the substrate for nitric oxide synthase), in the presence and absence halothane. RESULTS Electrical field stimulation produced frequency-dependent relaxations that were attenuated by inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester [L-NAME] or NG-monomethyl-L-arginine, 10(-4) M). Pretreatment with L-arginine (10(-4) M) prevented the effect of L-NAME. Halothane (0.5% or 1.0%) neither enhanced nor attenuated nonadrenergic, noncholinergic relaxations in the presence of L-NAME, D-NAME, L-arginine, or D-arginine. CONCLUSIONS Halothane, at concentrations < or = 1.0%, does not relax porcine airway smooth Muscle in vitro by activating the nonadrenergic, noncholinergic inhibitory system.
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impaired beta adrenergic receptor activation of adenylyl cyclase in airway smooth Muscle in the basenji greyhound dog model of airway hyperresponsiveness
American Journal of Respiratory Cell and Molecular Biology, 1993Co-Authors: C W Emala, Michael A Levine, Cynthia Black, Craig Curry, Carol A HirshmanAbstract:Previous studies in human asthmatics have suggested a defect in the beta-adrenergic pathway leading to cyclic adenosine monophosphate (cAMP) generation. Although these studies have suggested normal or increased numbers of beta-adrenergic receptors, limitations in the quantity of tissue available have not allowed further delineation of the biochemical or molecular mechanisms of human asthma. The basenji-greyhound (BG) dog model of nonspecific airway hyperreactivity displays similarities to human asthma, and altered functional response to beta-adrenergic agonists has been previously shown in airway tissue from this model. We have now correlated this functional impairment in beta-adrenergic response with a decreased generation of cAMP in response to isoproterenol. Organ bath studies and adenylyl cyclase assays of Trachealis Muscle revealed impaired responses to isoproterenol in the BG dog as compared with control dogs. Pretreatment of Muscle strips from BG dogs with isoproterenol had no effect on subsequent dose-response curves to methacholine (pD2 = 7.17 +/- 0.13, 7.34 +/- 0.12, and 7.14 +/- 0.17 for control, 10(-6) M isoproterenol, and 10(-5) M isoproterenol, respectively), while Muscle strips from mongrel dogs had a significant shift in methacholine responses after isoproterenol pretreatment (pD2 = 7.91 +/- 0.23, 7.48 +/- 0.29, and 6.98 +/- 0.33 for control, 10(-6) M isoproterenol, and 10(-5) M isoproterenol, respectively). Adenylyl cyclase activity in response to isoproterenol was 54% in the BG Trachealis membranes as compared with mongrels. Functional and biochemical responses to forskolin, NaF, prostaglandin, and dibutyryl cAMP, and the quantity of G,alpha were similar in the BG and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Peter D Pare - One of the best experts on this subject based on the ideXlab platform.
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canine Trachealis Muscle shortening and cartilage mechanics
Journal of Applied Physiology, 2004Co-Authors: Philip J Robinson, Robert R Schellenberg, Y Wakai, Jeremy Road, Peter D PareAbstract:Canine Trachealis Muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, Trachealis Muscle will shorten by only 30–40% when stimulated in vivo. To examine the...
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in vivo and in vitro correlation of Trachealis Muscle contraction in dogs
Journal of Applied Physiology, 1992Co-Authors: Mitsushi Okazawa, Robert R Schellenberg, Jeremy Road, K Ishida, Peter D PareAbstract:Maximal Trachealis Muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the Muscle was evaluated in vitro. In vivo Trachealis Muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis Muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the Trachealis Muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.
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effect of vagal stimulation and parenteral acetylcholine on canine Trachealis Muscle shortening
Journal of Applied Physiology, 1992Co-Authors: Mitsushi Okazawa, Y Wakai, Peter D Pare, S Osborne, Jeremy RoadAbstract:Canine Trachealis smooth Muscle shortening (TMS) in response to vagal nerve stimulation is approximately 30%, far less than the 70% predicted from in vitro studies. We hypothesized that in vivo airway smooth Muscle activation during vagal stimulation may be submaximal, and in this study we wished to determine TMS during maximal activation. TMS was studied in 12 alpha-chloralose-anesthetized dogs during vagal stimulation, systemic acetylcholine injection, and local acetylcholine injection. Bilateral vagal stimulation produced TMS of 26 +/- 5% (SE) length at functional residual capacity (LFRC). Maximal TMS during systemic injection of acetylcholine was 28 +/- 12% LFRC but may have been limited by delivery of acetylcholine to the Muscle because asystole occurred at higher concentrations. TMS was greatest during local injection of acetylcholine (48 +/- 7% LFRC). There was a greater increase in pulmonary resistance and decrease in dynamic compliance during systemic acetylcholine injection than during vagal stimulation. We conclude that bilateral vagal nerve stimulation does not maximally activate Trachealis smooth Muscle but that the maximal shortening achieved with local injection of acetylcholine is still less than isotonic shortening in vitro. These data suggest that maximal shortening in vivo is limited by the afterload provided by the tracheal cartilaginous rings.
Jeanpierre Bourreau - One of the best experts on this subject based on the ideXlab platform.
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control of the mode of excitation contraction coupling by ca2 stores in bovine Trachealis Muscle
American Journal of Physiology-lung Cellular and Molecular Physiology, 2000Co-Authors: Liang Tao, Yu Huang, Jeanpierre BourreauAbstract:Full muscarinic stimulation in bovine tracheal smooth Muscle caused a sustained contraction and increase in intracellular Ca2+concentration ([Ca2+]i) that was largely resistant to inhibition by nif...
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efficacy of muscarinic stimulation and mode of excitation contraction coupling in bovine Trachealis Muscle
Life Sciences, 2000Co-Authors: S Shen, Yu Huang, Jeanpierre BourreauAbstract:We have compared the efficacy of cromakalim and nifedipine to inhibit acetylcholine (ACh) and pilocarpine-induced tonic contractions in control preparations and in tissues where a fraction of the muscarinic receptor population had been removed by alkylation with phenoxybenzamine (PBZ). Both agonists induced contractions by stimulating pharmacologically similar receptors, probably of the M3 muscarinic subtype. The receptor reserve was larger, and the coupling between stimulation and contraction (E-C coupling) more efficient when ACh was the stimulating agonist. For stimulations that produced equal levels of Muscle response, cromakalim was more efficacious in inhibiting contractions induced by pilocarpine. The efficacy of cromakalim in relaxing contractions induced by ACh increased when the number of functional receptors decreased. Cromakalim and nifedipine decreased the efficiency of E-C coupling for ACh and pilocarpine. Cromakalim efficacy decreased in a sigmoid manner when stimulating concentrations of ACh (and receptor occupancy) increased, and there was an inverse relationship between receptor occupancy by ACh and cromakalim efficacy. In the presence of TEA, a K+ channel blocker, nifedipine almost completely inhibited contractions induced by the M3 muscarinic agonist bethanechol. These data indicate that in bovine tracheal smooth Muscle, electro-mechanical coupling is an inherent part of muscarinic E-C coupling, but its functional expression is dependent upon the efficacy of stimulation. The data also suggest that the M3 receptor is coupled to a cellular pathway linked with the activation of K+ channels that exerts a potent functional antagonism against activation of voltage-dependent Ca2+ entry.
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two distinct pathways for refilling ca2 stores in permeabilized bovine Trachealis Muscle
Life Sciences, 1999Co-Authors: Y Qian, Jeanpierre BourreauAbstract:Abstract Calcium entry from extracellular space to acetylcholine (ACh)-sensitive internal stores was investigated in β-escin permeabilized bovine tracheal smooth Muscle. Cyclopiazonic acid (CPA), a selective inhibitor of the sarcoplasmic reticulum (SR) calcium pump, and nifedipine, both inhibited the refilling, and inhibition was larger when these compounds were used simultaneously. BayK 8644 enhanced the refilling and completely reversed the inhibition induced by cyclopiazonic acid. In pCa 7 solution containing CPA, there was a spontaneous time-dependent decrease of ACh-induced transient contraction. In the presence of nifedipine or verapamil in the incubation solution reduced this time-dependent decrease in contractile responses to ACh stimulation, suggesting that these calcium-entry blockers decreased calcium leakage from internal stores to the extracellular space. These results suggest that in addition to the active calcium uptake in the SR, another pathway controlled by an L-type like calcium channel (dihydropyridine-sensitive) may exist between the extracellular compartment and the lumen of the SR in airway smooth Muscle, and contributes significantly to the loading of ACh-sensitive calcium stores.
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probing excitation contraction coupling in Trachealis smooth Muscle with the mycotoxin cyclopiazonic acid
Clinical and Experimental Pharmacology and Physiology, 1996Co-Authors: Daniel Amoako, Yun Qian, Chiuyin Kwan, Jeanpierre BourreauAbstract:1. Muscarinic stimulation-induced tonic contraction of airway smooth Muscle is independent of membrane potential. This contraction is not sensitive to inhibition by voltage-operated Ca2+ channel blockers or by K+ channel openers. 2. Cyclopiazonic acid (CPA) inhibits Ca2+ loading of internal stores but does not affect maximal tonic contraction induced by acetylcholine (ACh) in steady state conditions. 3. After depletion of internal Ca2+ stores with CPA, ACh-induced tonic contraction becomes dependent upon values of membrane potential. The contraction is then sensitive to voltage-operated Ca2+ channel blockers and to K+ channel openers. 4. Treatment of Trachealis Muscle with CPA potentiates the M2-mediated component of ACh stimulation, but this potentiation is not entirely responsible for the switch in excitation-contraction (E-C) coupling. 5. It is proposed that depletion of internal Ca2+ stores with CPA and promotion of M2-stimulation can lead to a switch in E-C coupling in Trachealis smooth Muscle from pharmaco- to electromechanical mode, perhaps by targeting a plasma membrane K+ channel.
C W Emala - One of the best experts on this subject based on the ideXlab platform.
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basenji greyhound dog increased m2 muscarinic receptor expression in Trachealis Muscle
American Journal of Physiology-lung Cellular and Molecular Physiology, 1995Co-Authors: C W Emala, A Aryana, Michael A Levine, Robert P Yasuda, S A Satkus, B B Wolfe, Carol A HirshmanAbstract:Airway smooth Muscle from asthmatic humans and from the Basenji-greyhound dog (BG) dog is hyporesponsive to beta-adrenergic agonist stimulation. Because adenylyl cyclase is under dual regulation in airway smooth Muscle, we compared muscarinic receptor-coupled inhibition of adenylyl cyclase in airway smooth Muscle from BG and mongrel dogs. Inhibition of forskolin-stimulated adenylyl cyclase activity by the muscarinic M2 agonist oxotremorine was greater in airway smooth Muscle membranes from BG compared with mongrel controls. Quantitative immunoprecipitation studies showed increased numbers of m2 but not m3 muscarinic receptors in the BG airway smooth Muscle. The enhanced ability of muscarinic agonists to inhibit adenylyl cyclase in BG airway smooth Muscle may be due to the greater numbers of muscarinic m2 receptors, which may account in part for impaired airway smooth Muscle relaxation in the BG model of airway hyperresponsiveness.
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impaired beta adrenergic receptor activation of adenylyl cyclase in airway smooth Muscle in the basenji greyhound dog model of airway hyperresponsiveness
American Journal of Respiratory Cell and Molecular Biology, 1993Co-Authors: C W Emala, Michael A Levine, Cynthia Black, Craig Curry, Carol A HirshmanAbstract:Previous studies in human asthmatics have suggested a defect in the beta-adrenergic pathway leading to cyclic adenosine monophosphate (cAMP) generation. Although these studies have suggested normal or increased numbers of beta-adrenergic receptors, limitations in the quantity of tissue available have not allowed further delineation of the biochemical or molecular mechanisms of human asthma. The basenji-greyhound (BG) dog model of nonspecific airway hyperreactivity displays similarities to human asthma, and altered functional response to beta-adrenergic agonists has been previously shown in airway tissue from this model. We have now correlated this functional impairment in beta-adrenergic response with a decreased generation of cAMP in response to isoproterenol. Organ bath studies and adenylyl cyclase assays of Trachealis Muscle revealed impaired responses to isoproterenol in the BG dog as compared with control dogs. Pretreatment of Muscle strips from BG dogs with isoproterenol had no effect on subsequent dose-response curves to methacholine (pD2 = 7.17 +/- 0.13, 7.34 +/- 0.12, and 7.14 +/- 0.17 for control, 10(-6) M isoproterenol, and 10(-5) M isoproterenol, respectively), while Muscle strips from mongrel dogs had a significant shift in methacholine responses after isoproterenol pretreatment (pD2 = 7.91 +/- 0.23, 7.48 +/- 0.29, and 6.98 +/- 0.33 for control, 10(-6) M isoproterenol, and 10(-5) M isoproterenol, respectively). Adenylyl cyclase activity in response to isoproterenol was 54% in the BG Trachealis membranes as compared with mongrels. Functional and biochemical responses to forskolin, NaF, prostaglandin, and dibutyryl cAMP, and the quantity of G,alpha were similar in the BG and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Jeremy Road - One of the best experts on this subject based on the ideXlab platform.
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canine Trachealis Muscle shortening and cartilage mechanics
Journal of Applied Physiology, 2004Co-Authors: Philip J Robinson, Robert R Schellenberg, Y Wakai, Jeremy Road, Peter D PareAbstract:Canine Trachealis Muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, Trachealis Muscle will shorten by only 30–40% when stimulated in vivo. To examine the...
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in vivo and in vitro correlation of Trachealis Muscle contraction in dogs
Journal of Applied Physiology, 1992Co-Authors: Mitsushi Okazawa, Robert R Schellenberg, Jeremy Road, K Ishida, Peter D PareAbstract:Maximal Trachealis Muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the Muscle was evaluated in vitro. In vivo Trachealis Muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis Muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the Trachealis Muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.
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effect of vagal stimulation and parenteral acetylcholine on canine Trachealis Muscle shortening
Journal of Applied Physiology, 1992Co-Authors: Mitsushi Okazawa, Y Wakai, Peter D Pare, S Osborne, Jeremy RoadAbstract:Canine Trachealis smooth Muscle shortening (TMS) in response to vagal nerve stimulation is approximately 30%, far less than the 70% predicted from in vitro studies. We hypothesized that in vivo airway smooth Muscle activation during vagal stimulation may be submaximal, and in this study we wished to determine TMS during maximal activation. TMS was studied in 12 alpha-chloralose-anesthetized dogs during vagal stimulation, systemic acetylcholine injection, and local acetylcholine injection. Bilateral vagal stimulation produced TMS of 26 +/- 5% (SE) length at functional residual capacity (LFRC). Maximal TMS during systemic injection of acetylcholine was 28 +/- 12% LFRC but may have been limited by delivery of acetylcholine to the Muscle because asystole occurred at higher concentrations. TMS was greatest during local injection of acetylcholine (48 +/- 7% LFRC). There was a greater increase in pulmonary resistance and decrease in dynamic compliance during systemic acetylcholine injection than during vagal stimulation. We conclude that bilateral vagal nerve stimulation does not maximally activate Trachealis smooth Muscle but that the maximal shortening achieved with local injection of acetylcholine is still less than isotonic shortening in vitro. These data suggest that maximal shortening in vivo is limited by the afterload provided by the tracheal cartilaginous rings.
