Role of PKC, tyrosine kinases, and Rho kinase in α-adrenoreceptor-mediated PASM contraction
| Autor: | Si-Oh Kim, Paul A. Murray, Noriaki Kanaya, Derek S. Damron, Yasuyuki Homma |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Myofilament Contraction (grammar) Vascular smooth muscle Physiology In Vitro Techniques Protein Serine-Threonine Kinases Pulmonary Artery Muscle Smooth Vascular Potassium Chloride Phenylephrine Dogs Physiology (medical) Internal medicine medicine Animals Rho-associated protein kinase Protein kinase C rho-Associated Kinases Chemistry Intracellular Signaling Peptides and Proteins Reproducibility of Results Cell Biology Protein-Tyrosine Kinases Receptors Adrenergic alpha Cell biology Endocrinology medicine.symptom Adrenergic alpha-Agonists Protein Kinases Tyrosine kinase Intracellular Vasoconstriction Muscle Contraction |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 283:L1051-L1064 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00345.2001 |
| Popis: | Our objectives were to identify the relative contributions of intracellular free Ca2+concentration ([Ca2+]i) and myofilament Ca2+sensitivity in the pulmonary artery smooth muscle (PASM) contractile response to the α-adrenoreceptor agonist phenylephrine (PE) and to assess the role of PKC, tyrosine kinases (TK), and Rho kinase (ROK) in that response. Our hypothesis was that multiple signaling pathways are involved in the regulation of [Ca2+]i, myofilament Ca2+sensitization, and vasomotor tone in response to α-adrenoreceptor stimulation of PASM. Simultaneous measurement of [Ca2+]iand isometric tension was performed in isolated canine pulmonary arterial strips loaded with fura 2-AM. PE-induced tension development was due to sarcolemmal Ca2+influx, Ca2+release from inositol 1,4,5-trisphosphate-dependent sarcoplasmic reticulum Ca2+stores, and myofilament Ca2+sensitization. Inhibition of either PKC or TK partially attenuated the sarcolemmal Ca2+influx component and the myofilament Ca2+sensitizing effect of PE. Combined inhibition of PKC and TK did not have an additive attenuating effect on PE-induced Ca2+sensitization. ROK inhibition slightly decreased [Ca2+]ibut completely inhibited myofilament Ca2+sensitization. These results indicate that PKC and TK activation positively regulate sarcolemmal Ca2+influx in response to α-adrenoreceptor stimulation in PASM but have relatively minor effects on myofilament Ca2+sensitivity. ROK is the predominant pathway mediating PE-induced myofilament Ca2+sensitization. |
| Databáze: | OpenAIRE |
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