Abstract
The adrenergic receptors play a key role in the modulation of sympathetic nervous system activity as well as a site of action for many therapeutic agents. The α1-adrenergic receptor subtypes (α1A-, α1B-, α1D) are the prime mediators of smooth muscle contraction and hypertrophic growth, but their characterization in both binding and function have lagged the other adrenergic family members. Although they are derived from a related ancestral gene and all nine adrenergic receptor family members bind the endogenous ligands, epinephrine and norepinephrine, with roughly similar affinities, there are major differences in the mode of binding, second messenger utilization, and physiological effects of the α1-subtypes compared with β- or α2-subtypes. Here, we review the recent literature on aspects of its binding pocket and how it differs from the β-adrenergic receptor paradigms. We also review the signaling components and aspects of its function and provide new insights into its roles in smooth muscle, growth, neurological, and cardiovascular function.
Footnotes
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Original work of the authors cited here was supported by National Institutes of Health Grants HL38120 (to M.T.P.) and HL61438 (to D.M.P.), the Southeast Affiliate of the American Heart Association (to M.T.P.), an American Heart Established Investigator Award (to D.M.P.), and an unrestricted research grant from Glaxo Wellcome (to D.M.P.).
- Abbreviations:
- GPCR
- G-protein-coupled receptor
- AR
- adrenergic receptor
- TM
- transmembrane
- CNS
- central nervous system
- [125I]HEAT
- (±)-β-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone
- GFP
- green fusion protein
- MSA
- multiple system atrophy
- MAPK
- mitogen-activated protein kinase
- ERK
- extracellular signal-regulated kinase
- JNK
- c-Jun N-terminal kinases
- Received January 31, 2001.
- Accepted March 14, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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