Abstract
The aim of the present study was to investigate if there is an altered expression of alpha-adrenoceptors during organ culture of rat mesenteric artery segments by using a sensitive pharmacological method and molecular biological techniques. Noradrenalin (NA) induced contraction via alpha1-adrenoceptors. The contraction and alpha1A-adrenoceptor mRNA levels were elevated during organ culture. Transcriptional inhibitor actinomycin D, translational inhibitor cycloheximide, protein kinase C inhibitors (staurosporine and RO31-8220) and mitogen-activated protein kinase (MAPK) pathway inhibitors (SB386023, U0126 and SB239063) prevented the increase in NA-induced contractions. The amount of alpha1A-adrenoceptor mRNA was significantly lower in the artery segments cultured for 1 day in the presence of specific MAPK extracellular signal-regulated protein kinase1/2 pathway inhibitor SB386023 than that of the cultured controls. SB386023 did not affect alpha2-adrenoceptor mRNA level. Our results suggest that the up-regulation of alpha1A-adrenoceptors involves transcription and intracellular signal transduction via the protein kinase C and the ERK 1/2 pathways.
| Original language | English |
|---|---|
| Journal | Basic & clinical pharmacology & toxicology |
| Volume | 98 |
| Issue number | 1 |
| Pages (from-to) | 61-7 |
| Number of pages | 7 |
| ISSN | 1742-7835 |
| DOIs | |
| Publication status | Published - Jan 2006 |
| Externally published | Yes |
Keywords
- Adrenergic alpha-Agonists
- Animals
- Enzyme Inhibitors
- Imidazoles
- Mesenteric Artery, Superior
- Mitogen-Activated Protein Kinases
- Norepinephrine
- Organ Culture Techniques
- Phosphorylation
- Protein Kinase C
- Pyrimidines
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Receptors, Adrenergic, alpha-1
- Signal Transduction
- Staurosporine
- Up-Regulation
- Vasoconstriction
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