Our body′s “fight or flight” response is regulated through a chemical called adrenaline released through nerve endings. Adrenaline works by attaching to proteins called receptors that are placed in essentially every organ and tissue throughout the body. How one drug can regulate all the organs in the body at the same time and do so in variant ways is through different adrenergic receptors called subtypes. I work on different adrenergic receptor subtypes and can demonstrate how one subtype can protect the heart against damage from heart attacks or can increase your ability to remember things by growing new neurons in the brain.
Our main focus is to discern the roles of three α1-adrenergic receptor subtypes (α1A, α1B and α1D) in physiological and pathophysiological states. All three subtypes are highly homologous in both structure and function, yet evidence suggests that each subtype may play unique roles in signaling and disease states. Our approaches are multi-faceted and multi-disciplined, involving transgenic and knockout mice. Our transgenic mouse models of the α1B subtype develop cardiac hypertrophy, hypotension, and neurodegeneration. However, the α1A subtype appears to be cardioprotective and neuroprotective. Transgenic mice of the α1A subtype protect against ischemic damage in the heart and can precondition against further damage. In the brain, the α1A subtype is anti-epileptic, increases cognitive functions and is involved in neurogenesis. Administration of an α1A agonist in the drinking water of normal mice increased learning and memory, in addition to increasing neurogenesis. Our work suggests that α1A agonists may offer new therapeutic treatments for cognitive decline, neurodegeneration and myocardial infarction.
Shi T, Papay RS & Perez DM. α1A-AR differentially regulates STAT3 phosphorylation through PKCε and PKCδ in myocytes. J Recept Signal Transduct Res 32:76, 2012.
Doze VA & Perez DM. G-Protein Coupled Receptors in Adult Neurogenesis. Pharm Rev 64:645, 2012.
Doze VA, Papay RS...Perez DM. Long term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood and longevity. Mol Pharmacol 80:747, 2011.
Perez DM & Doze VA. Cardiac and Neuroprotection Regulated by α1-Adrenergic Receptor Subtypes. J Recept Signal Transduct Res 31:98, 2011.
Perez DM, Papay RS, & Shi T. α1-Adrenergic Receptor Stimulates IL-6 Expression and Secretion through both mRNA Stability & Transcriptional Regulation: Involvement of p38 MAPK and NF-kB. Mol Pharmacol 76:144, 2009.