Effects of Direct and Indirect Activation of G Protein of Adenylyl Cyclase on the Subsequent Response to ß-Adrenergic Receptor Agonists in Human Trachealis
| Autor: | Kenichi Yamaki, Hiroaki Kume, Kenzo Takagi, Yukio Sudo, Satoru Ito, Yasushi Ito |
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| Rok vydání: | 2011 |
| Předmět: |
Agonist
Cholera Toxin medicine.medical_specialty Adrenergic receptor G protein medicine.drug_class Muscle Relaxation In Vitro Techniques medicine.disease_cause Bronchoconstrictor Agents Adenylyl cyclase chemistry.chemical_compound Internal medicine Isoprenaline Drug Discovery medicine Humans Receptor Methacholine Chloride Aged Aged 80 and over Cholera toxin Isoproterenol Muscle Smooth Adrenergic beta-Agonists Middle Aged Heterotrimeric GTP-Binding Proteins Enzyme Activation Trachea Endocrinology chemistry Formoterol Muscle Contraction medicine.drug |
| Zdroj: | Arzneimittelforschung. 52:803-812 |
| ISSN: | 1616-7066 0004-4172 |
| DOI: | 10.1055/s-0031-1299971 |
| Popis: | To examine the response to beta-adrenergic receptor agonists (beta-agonists) following prolonged activation of the stimulatory G protein of adenylyl cyclase (Gs), relaxation by isoproterenol (isoprenaline, CAS 949-36-0) and formoterol (CAS 73573-87-2), a long-acting beta-agonist, after exposure to formoterol was measured in human tracheal smooth muscle, using isometric tension records. Prior exposure to formoterol (0.3-30 nmol/l) for 45 min reduced the subsequent relaxation induced by this drug in a concentration-dependent manner, but only modestly reduced that induced by isoproterenol. Next, the effects of cholera toxin (CTX, CAS 9012-63-9) an irreversible direct activator of Gs and formoterol on the reduced responsiveness to isoproterenol after continuous and repeated exposure to isoprotenerol were examined. Preincubation with cholera toxin (0.02-2 micrograms/ml) caused concentration-dependent inhibition of the desensitization induced by isoproterenol, but preincubation with formoterol did not. These results indicate that prolonged activation of Gs via beta-adrenergic receptors does not cause cross-desensitization to short-acting beta-agonists. However, it also fails to inhibit the desensitization of beta-adrenergic receptors after excessive exposure to short-acting beta-agonists. Activation of Gs via a pathway that bypasses the receptors may be beneficial for the prevention of this phenomenon. |
| Databáze: | OpenAIRE |
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