Molecular pharmacology of the G protein-coupled receptors, adrenergic receptors and adrenomedullin and calcitonin gene-related peptide receptors.
G protein-coupled receptors such as adrenergic receptors and adrenomedullin and calcitonin gene-related peptide receptors are directly involved in regulating the cardiovascular system via such mechanisms as vasoconstriction or vasodilation respectively of the vasculature. Our laboratory has cloned and characterized ?1 adrenergic receptor subtypes and their alternatively spliced gene transcripts from rodent species such as the rat and the gerbil. We have also investigated the distribution of these receptors in various organs including the heart, kidney, parotid and cochlea using the quantitative reverse transcriptase polymerase chain reaction in order to ascertain the role of these receptors in these organs. The adrenomedullin and calcitonin gene-related peptide receptors have also been characterized in tissues with respect to gene transcripts and pharmacological characteristics with the goal of distinguishing receptor subtypes and their respective functions in various tissues. Both of these receptors have identical G protein-coupled receptors but their pharmacological properties are determined by various accessory proteins, receptor activity-modifying proteins. We have discovered and cloned splice variants for the receptor activity-modifying proteins and are using signal transduction assays and immunofluorescence to investigate how these spliced transcripts affect the pharmacology of these receptors.
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