Beta-adrenergní receptory a jejich desenzitizace

Biriczová, Lilla

β-Adrenergic receptors (β-ARs) are G-protein-coupled receptors (GPCR), widely present in the animal organism and mediate catecholamine pathways leading to diverse physiological responses. The family of β-ARs consists of β1-AR, β2-AR and β3-AR, which are distinguished by their affinity to adrenaline and noradrenaline. A typical model of β-AR signalling includes binding of the ligand, G-protein coupling, activation of adenylyl cyclase (AC) resulting in production of the second messenger cAMP and activation of protein kinase A (PKA) that phosphorylates downstream proteins leading to physiological responses. Beacause excessive catecholamine signalling can cause undesirable consequences, a mechanism has evolved, which attenuates the function of β-ARs in spite of further stimulation, so called desensitization. The classic course of desensitization consists of characteristic steps including phosphorylation of the receptor, β-arrestin attachement and uncoupling of the G-protein from β-AR. Restoration of the signalling ability is allowed through resensitization of β-AR when the receptor is sequestrated and dephosphorylated. Given that β-ARs are structurally and genetically different, it is reasonable to consider that each step of the desenstization process may happen differently among the different subtypes...

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