Mechanical strain modulates maximal phosphatidylinositol turnover in airway smooth muscle.
Mechanical strain regulates the maximal level of myosin light chain phosphorylation mediated by muscarinic activation in airway smooth muscle. Accordingly, we tested the hypothesis that mechanical strain regulates maximal phosphatidylinositol (PI) turnover (V(max)) coupled to muscarinic receptors in bovine tracheal smooth muscle. We found that PI turnover was not significantly length dependent in unstimulated tissues. However, carbachol-induced PI turnover was linearly dependent on muscle length at both 1 and 100 microM. The observed linear length dependence of PI turnover at maximal carbachol concentration (100 microM) suggests that mechanical strain regulates V(max). When carbachol concentration-PI turnover relationships were measured at optimal length and at 20% optimal length, the results could be explained by changes in V(max) alone. To determine whether the length-dependent step is upstream from heterotrimeric G proteins, we investigated the length dependence of fluoroaluminate-induced PI turnover. The results indicate that fluoroaluminate-induced PI turnover remained significantly length dependent at maximal concentration. These findings together suggest that regulating functional units of G proteins and/or phospholipase C enzymes may be the primary mechanism of mechanosensitive modulation in airway smooth muscle.
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Department of Molecular Pharmacology, Brown University, Providence, Rhode Island 02912, USA.
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D000109:Acetylcholine / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D005461:Fluorine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000493:pharmacokinetics; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D014132:Trachea / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D014316:Tritium; D014665:Vasodilator Agents / Q000494:pharmacology
D018679:Cholinergic Agonists; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D014665:Vasodilator Agents; D014316:Tritium; C053629:fluoroaluminum; D005461:Fluorine; D002217:Carbachol; D000535:Aluminum; D019204:GTP-Binding Proteins; D000109:Acetylcholine