دورية أكاديمية
Differential Rho-kinase dependency of full and partial muscarinic receptor agonists in airway smooth muscle contraction
| العنوان: | Differential Rho-kinase dependency of full and partial muscarinic receptor agonists in airway smooth muscle contraction |
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| المؤلفون: | Schaafsma, D, Boterman, M, de Jong, A-M, Hovens, I., Penninks, JM, Nelemans, SA, Meurs, H, Zaagsma, J |
| المصدر: | Schaafsma , D , Boterman , M , de Jong , A-M , Hovens , I , Penninks , JM , Nelemans , SA , Meurs , H & Zaagsma , J 2006 , ' Differential Rho-kinase dependency of full and partial muscarinic receptor agonists in airway smooth muscle contraction ' , British Journal of Pharmacology , vol. 147 , no. 7 , pp. 737-743 . https://doi.org/10.1038/sj.bjp.0706665Test |
| سنة النشر: | 2006 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Rho-kinase, airway smooth muscle, contraction, Ca2+-mobilization, Ca2+-influx, Ca2+-sensitization, bovine, muscarinic agonists, muscarinic receptors, Y-27632, PHOSPHOINOSITIDE METABOLISM, MYOSIN PHOSPHORYLATION, CA2+ SENSITIVITY, CELLS, SENSITIZATION, MOBILIZATION, ACTIVATION, GENERATION, SUBTYPE, CALCIUM |
| الوصف: | 1 In airway smooth muscle (ASM), full and partial muscarinic receptor agonists have been described to have large differences in their ability to induce signal transduction, including Ca2+-mobilization. Despite these differences, partial agonists are capable of inducing a submaximal to maximal ASM contraction. 2 To further elucidate transductional differences between full and partial muscarinic receptor agonists, we investigated the contribution of Rho-kinase ( an important regulator of Ca2+-sensitization) to methacholine-, pilocarpine- and McN-A-343-induced bovine tracheal smooth muscle (BTSM) contraction, using the selective Rho-kinase inhibitor Y-27632. In addition, we measured Ca2+-mobilization and - influx in BTSM cells in response to these agonists in the absence and presence of Y-27632. 3 Whereas treatment with Y-27632 ( 1 mu M) significantly decreased potency (pEC(50)) for all agonists, maximal contraction (E-max) was reduced by 23.4 +/- 2.8 and 50.4 +/- 7.9% for the partial agonists pilocarpine and McN-A-343, respectively, but was unaffected for the full agonist methacholine. However, E-max of methacholine became Rho-kinase dependent after taking away its receptor reserve using the irreversible muscarinic receptor antagonist propylbenzilylcholine mustard. 4 Pilocarpine and McN-A-343 induced a very small Ca2+-mobilization and - influx as compared to methacholine. In addition, an inverse relationship of these two parameters with the Rho-kinase dependency was observed. Interestingly, no inhibitory effects of Y-27632 were observed on Ca2+-mobilization and-influx for all three agonists, indicating that the effects of Y-27632 on contraction are most likely on the level of Ca2+-sensitization. 5 In conclusion, in contrast to the full agonist methacholine, the partial muscarinic receptor agonists pilocarpine and McN-A-343 are dependent on Rho-kinase for their maximal contractile effects, presumably as a consequence of differences in transductional reserve, indicating an agonist-dependent role for Rho-kinase in ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/a39853eb-f248-45d0-a10c-3a23d8ca9366Test |
| DOI: | 10.1038/sj.bjp.0706665 |
| الإتاحة: | https://doi.org/10.1038/sj.bjp.0706665Test https://hdl.handle.net/11370/a39853eb-f248-45d0-a10c-3a23d8ca9366Test https://research.rug.nl/en/publications/a39853eb-f248-45d0-a10c-3a23d8ca9366Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.D942D25 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/sj.bjp.0706665 |
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