Abstract
α1-adrenergic receptors are G-Protein Coupled Receptors that are involved in neurotransmission and regulate the sympathetic nervous system through binding and activating the neurotransmitter, norepinephrine, and the neurohormone, epinephrine. There are three α1-adrenergic receptor subtypes (α1A, α1B, α1D) that are known to play various roles in neurotransmission and cognition. They are related to two other adrenergic receptor families that also bind norepinephrine and epinephrine, the β- and α2-, each with three subtypes (β1, β2, β3, α2A, α2B, α2C). Previous studies assessing the roles of α1-adrenergic receptors in neurotransmission and cognition have been inconsistent. This was due to the use of poorly-selective ligands and many of these studies were published before the characterization of the cloned receptor subtypes and the subsequent development of animal models. With the availability of more-selective ligands and the development of animal models, a clearer picture of their role in cognition and neurotransmission can be assessed. In this review, we highlight the significant role that the α1-adrenergic receptor plays in regulating synaptic efficacy, both short and long-term synaptic plasticity, and its regulation of different types of memory. We will also present evidence that the α1-adrenergic receptors, and particularly the α1A-adrenergic receptor subtype, are a potentially good target to treat a wide variety of neurological conditions with diminished cognition.
Highlights
Raymond Ahlquist in 1948 (Ahlquist, 1948) first introduced the concept of different types of receptors called adrenergic receptors (ARs) which are activated by the same catecholamines, epinephrine (Epi) and norepinephrine (NE), but displayed opposite phenotypes in the body
The regulation of neurogenesis by the a1A-AR may play a role in its synaptic plasticity, regulation of cognition, and therapeutics designed to activate this receptor subtype may provide some repair to the neurodegeneration that occurs in Alzheimer’s Disease
The a1A-AR transgenic displayed increased cognition in a battery of electrophysiological tests, such as basal synaptic transmission, paired-pulse facilitation (PPF), and long-term potentiation (LTP) compared with WT mice, consistent with the increased cognition displayed through behavioral studies (Doze et al, 2011)
Summary
Raymond Ahlquist in 1948 (Ahlquist, 1948) first introduced the concept of different types of receptors called adrenergic receptors (ARs) which are activated by the same catecholamines, epinephrine (Epi) and norepinephrine (NE), but displayed opposite phenotypes in the body. He assigned them the subtypes of a and b. A few years later, another receptor was cloned that displayed novel pharmacology from the previous two subtypes and was named the a1D-AR (Perez et al, 1991) This classification of a1-ARs subtypes was approved by the IUPHAR Adrenergic Receptor Subcommittee in 1995 (Hieble et al, 1995). These two b2-AR agonists display 1,000-fold selectivity over the b1-AR by virtue of their ability to bind to the lipophilic transmembrane domains and increasing duration of action and are used clinically as bronchodilators to treat asthma (Lindén et al, 1996; Baker et al, 2015)
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