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Guinea-pig Tracheal Smooth Muscle (guinea-pig + tracheal_smooth_muscle)

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Medical Sciences	100%

Selected Abstracts

Evidence showing that ,-adrenoceptor subtype responsible for the relaxation induced by isoprenaline is principally ,2 but not ,1 in guinea-pig tracheal smooth muscle

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2004
Y. Tanaka
Summary 1 The present study was carried out to pharmacologically identify the ,-adrenoceptor subtype that mediates isoprenaline-elicited relaxation in the isolated guinea-pig tracheal smooth muscle, to answer the question whether it is ,1 - or ,2 -subtype? 2 Isoprenaline as well as salbutamol, a well-known ,2 -selective adrenoceptor agonist, produced a concentration-dependent relaxation with a pD2 value of 8.12 vs. 7.54 for salbutamol. 3 Isoprenaline-elicited relaxation was not affected by ,1 -selective antagonists, atenolol and CGP-20,712A, within the concentration ranges supposed to antagonize ,1 -subtype: atenolol, ,10,6 m; CGP-20,712A, ,10,8 m. 4 By contrast, the concentration,response curves for isoprenaline as well as salbutamol were shifted rightwards in a competitive fashion by atenolol at the concentrations ,3 × 10,6 m. However, pA2 values of atenolol against isoprenaline (5.86) and salbutamol (5.71) were consistent with the value corresponding to ,2 - but not to ,1 -subtype (around 7.00), and these values were not significantly different from each other. 5 Competitive antagonism of the relaxations to isoprenaline and salbutamol were also obtained with ,2 -selective antagonists, butoxamine and ICI-118,551. Against isoprenaline and salbutamol, the pA2 values of butoxamine (6.51 vs. 6.81) and ICI-118,551 (8.83 vs. 8.90) were substantially identical. Thus the primary mediation of ,2 -receptor in the relaxations was strongly supported. 6 The present findings provide evidence that the ,-adrenoceptor which mediates isoprenaline-elicited relaxation of guinea-pig tracheal smooth muscle is essentially ,2 - but not ,1 -subtype. The present study also indicates the importance of using multiple receptor antagonists with different pA2 values to pharmacologically identify the responsible receptor subtype in smooth muscle mechanical responses. [source]

Roles of P2X receptors and Ca2+ sensitization in extracellular adenosine triphosphate-induced hyperresponsiveness in airway smooth muscle

CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2007
T. Oguma
Summary Background The release of adenosine triphosphate (ATP) from the airway epithelial cells during the inflammatory process is considered to play an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease. Objective This study was designed to determine whether extracellular ATP is involved in the bronchial hyperresponsiveness as an interaction between epithelium and smooth muscle in the airways. Methods We examined the contractile response to methacholine (MCh) before and after exposure to low concentrations (10 ,m) of ATP in isolated, epithelium-denuded guinea-pig tracheal smooth muscle by measuring isometric tension. Intracellular Ca2+ concentrations ([Ca2+]i) were assessed by fluorescent intensities of fura-2. Results MCh-induced contractile force was increased with no change in [Ca2+]i after exposure to 10 ,m ATP for 15 min. The ability of ATP to enhance the MCh-induced contraction was markedly attenuated by suramin, a non-selective P2 receptor inhibitor. Pre-incubation with ATP,S, a non-hydrolysable analogue of ATP and ,,,-meATP, a P2X agonist, also enhanced the MCh-induced contraction. In contrast, uracil triphosphate, a P2Y agonist, did not affect the MCh-induced contraction. Y-27632, a Rho-kinase inhibitor, suppressed the ability of ATP to enhance the MCh-induced contraction. Moreover, PP1 and PP2, Src tyrosin kinase inhibitors, suppressed the enhancement of MCh-induced contraction by ATP. Conclusion Pre-treatment with ATP induces hyperresponsiveness to MCh mediated by Ca2+ sensitization via the P2X receptor in airway smooth muscle. The present findings suggest the possible involvement of both the Rho-kinase and Src pathways in the intracellular mechanism of this phenomenon. [source]

Tonic Potentiation And Attenuation Produced By Membrane Depolarization In Guinea-Pig Trachealis

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2000
Kenichi Yamaki
SUMMARY 1. We studied how membrane depolarization directly affected intracellular Ca2+ signalling when voltage-operated Ca2+ channels (VOCC) were not available in guinea-pig tracheal smooth muscle. To block VOCC, we used 3 ,mol/L verapamil, which completely abolished high K+ (20,60 mmol/L)-induced contraction, and elevation of fura-2 signal. 2. Muscle tone was generated by adding Ca2+ to the extracellular Ca2+ -free solution containing prostaglandin (PG)E2 (100 nmol/L) after abolishing basal tone with indomethacin (1 ,mol/L). 3. In the absence of verapamil, high K+ (20,60 mmol/L) solution potentiated 2.4 mmol/L Ca2+ -induced sustained contractions. Even in the presence of 3 ,mol/L verapamil, replacement with 20 and 40 mmol/L K+ solution induced tonic potentiation, which was changed to attenuation with a higher K+ solution (60 mmol/L), lower extracellular Ca2+ concentration ([Ca2+]o) and pretreatment with cyclopiazonic acid (10 ,mol/L), a Ca2+ sequestration inhibitor. 4. These results indicate that the balance between depolarization-dependent Ca2+ release and receptor-operated cation channel inhibition may determine whether tonic potentiation or attenuation is manifested, depending on the availability of VOCC, the magnitude of the depolarization, [Ca2+]o and Ca2+ content in the sarcoplasmic reticulum. [source]