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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Svensson, Carl-lennart Edvinsson, Lars Hansen-schwartz, Jacob Xu, Cang-bao |
| Description | Author Affiliation: Hansen-Schwartz J ( Department of Internal Medicine, Lund University Hospital, Lund, Sweden. jacob.schwartz@dadlnet.dk) |
| Abstract | 1. Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process. 2. The effect of inhibiting protein kinases during organ culture with staurosporine (unspecific protein kinase inhibitor), RO 31-7549 (specific inhibitor of classical PKC's) and H 89 (specific inhibitor of PKA) was examined using in vitro pharmacological examination of cultured vessel segments with ET-1 (unspecific ET(A) and ET(B) agonist), S6c (specific ET(B) agonist) and 5-CT (5-HT(1) agonist). Levels of mRNA coding for the ET(A), ET(B), 5-HT(1B) and 5-HT(1D) receptors were analysed using real-time RT-PCR. 3. Classical PKC's are critically involved in the appearance of the ET(B) receptor; co-culture with RO 31-7549 abolished the contractile response (6.9 +/- 1.8%) and reduced the ET(B) receptor mRNA by 44 +/- 4% as compared to the cultured control. Correlation between decreased ET(B) receptor mRNA and abolished contractile function indicates upstream involvement of PKC. 4. Inhibition of PKA generally had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5. Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had no significant effect on the mRNA levels of these receptors. This lack of correlation indicates an additional downstream involvement of protein kinases. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 137 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2002-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Basilar Artery Metabolism Cyclic AMP-Dependent Protein Kinases Protein Kinase C Receptors, Endothelin Receptors, Serotonin Sulfonamides Animals Drug Effects Physiology Antagonists & Inhibitors Indoles Pharmacology Isoquinolines Maleimides Muscle Contraction Muscle, Smooth, Vascular Organ Culture Techniques RNA, Messenger Rats, Inbred WKY Receptor, Endothelin A Receptor, Endothelin B Receptor, Serotonin, 5-HT1B Receptor, Serotonin, 5-HT1D Genetics Reverse Transcriptase Polymerase Chain Reaction Staurosporine Up-Regulation Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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