Relationship between α1-adrenergic receptor-induced contraction and extracellular signal-regulated kinase activation in the bovine inferior alveolar artery

Chris Hague, Pedro J. Gonzalez-Cabrera, William B. Jeffries, Peter W. Abel

Research output: Contribution to journalArticle

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Abstract

The endogenous adrenergic agonists norepinephrine (NE) and epinephrine regulate vascular tone by stimulating α1-adrenergic receptors (ARs) on smooth muscle cells to cause contraction. In addition, α1-ARs also couple to growth factor pathways, through stimulation of mitogen-activated protein kinases (MAPKs). MAPKs are a family of serine-threonine kinases that include extracellular signal-regulated kinase (ERK) and a variety of other kinases that are able to activate transcription factors when stimulated. We examined α1-AR stimulation of contraction and ERK activation in the bovine inferior alveolar artery (BIAA), using in vitro contraction studies and Western blotting. Using antagonists selective for individual adrenergic receptor types, we found that only α1-ARs were coupled to ERK activation and contraction. NE stimulated contraction (EC50 = 11 μM) and ERK activation (EC50 = 21 μM) with similar potency. Using α1-AR subtype-selective antagonists, we identified the α1-AR subtypes coupled to each response. Affinity values for α1-AR subtype-selective antagonists were consistent with α1-AR-mediated contraction. In contrast, simultaneous treatment with concentrations of these antagonists selective for each α1-AR subtype (α1A-, α1B-, and α1D-AR) was required to inhibit ERK activation, suggesting that all three α1-ARs activate ERK in BIAA. Transmural electrical stimulation of BIAA segments resulted in activation of ERK, which was inhibited by the α1-AR-selective antagonist BE 2254 (2-[[β-(4-hydroxyphenyl)ethyl]aminomethyl]-1-tetralone). These data suggest that in an intact artery, NE released from sympathetic nerves stimulates α1-ARs to cause contraction and ERK activation, and that redundancy among subtypes exists for α1-AR activation of ERK.

Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume303
Issue number1
DOIs
StatePublished - Oct 2002

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Extracellular Signal-Regulated MAP Kinases
Adrenergic Receptors
Arteries
Norepinephrine
Mitogen-Activated Protein Kinases
Tetralones
Adrenergic Agonists
Adrenergic Antagonists
Protein-Serine-Threonine Kinases
Electric Stimulation
Epinephrine
Smooth Muscle Myocytes
Blood Vessels
Intercellular Signaling Peptides and Proteins
Transcription Factors
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Relationship between α1-adrenergic receptor-induced contraction and extracellular signal-regulated kinase activation in the bovine inferior alveolar artery. / Hague, Chris; Gonzalez-Cabrera, Pedro J.; Jeffries, William B.; Abel, Peter W.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 303, No. 1, 10.2002, p. 403-411.

Research output: Contribution to journalArticle

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