Constitutive activity in orphan G protein coupled receptors

摘要: The goal of this research was to use a distal signaling pathway analysis evaluate the extent agonist independent constitutive among orphan class-A G protein coupled receptors (GPCRs). These translate extracellular signals via conformational change into intracellular activation different proteins and subsequent second messenger synthesis. small molecules regulate cellular biochemistry, eventually leading nuclear that results in changes gene expression. Some GPCRs are capable absence an activating ligand, phenomenon called activity is inhibited “inverse-agonist”. cAMP dependent Luciferase expression used compare canonical all five wild-type Muscarinic Acetylcholine their constitutively active (CA) mutant counterparts. All members, both CA, signaled pathways, although only CA mutants do so agonist. This technique then applied 40 for which unknown/not-present. resulted 75% (30 out 40) scoring as active, grouped categories based on response. largest most significant group 17 orphans expression, basal forskolin stimulated, by more than 40%, indicating Gαi. In total, novel findings were found 23 Orphan with otherwise agreement literature cases. closely related amino acid homology tended have similar effects suggest identification inverse agonists may be fruitful approach categorizing these targeting them pharmacological intervention.