Evidence that simulated microgravity may alter the vascular nonreceptor tyrosine kinase second messenger pathway
| Autor: | C I, Kahwaji, S, Sheibani, S, Han, W O, Siu, A H, Kaka, T M, Fathy, N H, el-Abbadi, R E, Purdy |
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| Rok vydání: | 2000 |
| Předmět: |
Flavonoids
Male Weightlessness Parasympatholytics Receptor Protein-Tyrosine Kinases Protein-Tyrosine Kinases Genistein Second Messenger Systems Muscle Smooth Vascular Rats Hindlimb Suspension Calcium-Calmodulin-Dependent Protein Kinases Animals Aorta Abdominal Enzyme Inhibitors Rats Wistar Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Kinase C |
| Zdroj: | Proceedings of the Western Pharmacology Society. 43 |
| ISSN: | 0083-8969 |
| Popis: | Simulated microgravity (hind limb unweighting; HU) reduces maximal contractile capacity to norepinephrine (NE) but not 5-hydroxytryptamine (5-HT) in the rat abdominal aorta of male Wistar rats. Our earlier study showed that voltage-operated calcium channels, the MAPK pathway [1], and vasoconstrictive prostaglandins contribute to the NE-induced contraction of control (C) but not HU, aorta rings. Genistein, a general tyrosine kinase inhibitor, caused a significant reduction in vascular contractility in C but not HU arteries. The present study explored the role of protein kinase C (PKC) and extracellular receptor-activated kinase 1 and 2 (ERK1/2) in the HU-induced vascular hyporesponsiveness to NE. Microgravity was simulated in Wistar rats by 20 day HU. The abdominal aorta was removed from control and HU rats, cut into 3 mm rings, and mounted in tissue baths to measure isometric contraction. Protein levels were determined using Western blot analysis. PD98059, a selective MAPKK inhibitor, caused a marked inhibition of NE-induced contraction in both C and HU arteries. Calphostin C, a PKC inhibitor, completely abolished the contractile response to NE in both C and HU tissues. Phosphorylated (activated) ERK1/2 protein mass was greater in C, compared to HU, aortas, and was reduced by genistein only in C tissues. MAPK total protein levels in the rat aorta were increased in the HU-treated, compared to C, animals. These results indicate that PKC represents an early transduction step in the contractile response to NE in the rat abdominal aorta. That inhibition of the step immediately before activation of MAPK reduced contraction in both C and HU tissues, while general tyrosine kinase inhibition with genistein blocked only the control responses, suggests that a nonreceptor tyrosine kinase may be involved in HU-induced vascular hyporesponsiveness to NE. |
| Databáze: | OpenAIRE |
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