Characterization of α₂-adrenergic receptor localization and functional responses
The three α₂-adrenergic receptors (α₂-ARs) were studied in both recombinant and endogenous systems. It was my general hypothesis that the three α₂-adrenergic receptor (AR) subtypes exhibit differential tissue and subcellular localization and couple to physiological pathways to directly elicit functional responses. It was our hope, that in identifying differences between the α₂-ARs we may elucidate their physiological roles and provide a potential means for the rational development of therapeutic drugs or models of such pathologies as atherosclerosis, hypertension and glaucoma. Subtype selective antibodies have been generated and these have provided a tool with which to study the receptors on a molecular and cellular level. Utilizing a number of biochemical, pharmacological, molecular and cellular techniques, I have identified differences between the three receptors with respect to the tissues in which they are expressed, the subcellular domains in which they localize and their patterns of sequestration and down-regulation. In addition, I have demonstrated the expression and co-localization of the α₂-ARs in a variety of native tissues, and a number of functional responses these receptors mediate. These functional responses may have ramifications relevant to tissue healing mechanisms as well as may play a role in a number of pathologies.
Biology, Molecular., Health Sciences, Pharmacology., Biology, Animal Physiology.
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