Role of phosphoinositide metabolism in human bronchial smooth muscle contraction and in functional antagonism by beta-adrenoceptor agonists
| Autor: | Van Amsterdam, R G, Meurs, H, Ten Berge, R E, Veninga, N C, Brouwer, F, Zaagsma, J, Schuiling-Veninga, Nynke |
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| Přispěvatelé: | Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC) |
| Jazyk: | angličtina |
| Rok vydání: | 1990 |
| Předmět: |
Pulmonary and Respiratory Medicine
Agonist Male medicine.medical_specialty Contraction (grammar) medicine.drug_class Bronchi In Vitro Techniques Phosphatidylinositols chemistry.chemical_compound Internal medicine Bronchodilation medicine Humans Inositol phosphate Methacholine Chloride Aged chemistry.chemical_classification Isoproterenol Smooth muscle contraction Middle Aged Endocrinology chemistry Methacholine medicine.symptom Histamine medicine.drug Muscle contraction Muscle Contraction |
| Zdroj: | American Review of Respiratory Disease, 142(5), 1124-1128 |
| ISSN: | 0003-0805 1124-1128 |
| Popis: | The aim of the present investigation was to study in human bronchial smooth muscle (1) the relationship between methacholine and histamine-induced inositol phosphate (IP) production and contraction, (2) the influence of increasing concentrations of methacholine and histamine on the relaxation (pD2 and Emax) by isoproterenol (functional antagonism), and (3) the relation between IP production by methacholine and histamine and the changes of pD2 and Emax values of isoproterenol-induced relaxation. Methacholine and histamine were full agonists in contracting human bronchial smooth muscle, with pD2 values of 6.01 +/- 0.18 and 6.07 +/- 0.04, respectively. With IP production, however, pD2 values of 4.90 +/- 0.06 for methacholine and 5.15 +/- 0.16 for histamine were obtained, indicating a considerable reserve of PI metabolism for contraction. With increasing concentrations of histamine and methacholine (to 1 and 0.1 mM, respectively), subsequently performed dose-relaxation curves with isoproterenol showed decreasing values of pD2 (from 8.25 +/- 0.20 to 7.28 +/- 0.28) and Emax (from 100% to 56.7 +/- 12.4%). No differences were observed between methacholine and histamine in this respect. A significant correlation was found between IP production induced by the various concentrations of methacholine and histamine and the reduction of isoproterenol pD2 and Emax values. The results strongly suggest that PI metabolism may play an important role in the reduced efficacy of beta-adrenoceptor agonists to induce bronchodilation during active and severe asthma. |
| Databáze: | OpenAIRE |
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