Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine

Abstract

Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor (α2AR) agonist currently used in clinical settings. Because DEX has dose-dependent advantages of sedation, analgesia, antianxiety, inhibition of sympathetic nervous system activity, cardiovascular stabilization, and significant reduction of postoperative delirium and agitation, but does not produce respiratory depression and agitation, it is widely used in clinical anesthesia and ICU departments. In recent years, much clinical study and basic research has confirmed that DEX has a protective effect on a variety of organs, including the nervous system, heart, lungs, kidneys, liver, and small intestine. It acts by reducing the inflammatory response in these organs, activating antiapoptotic signaling pathways which protect cells from damage. Therefore, based on wide clinical application and safety, DEX may become a promising clinical multiorgan protection drug in the future. In this article, we review the physiological effects related to organ protection in α2AR agonists along with the organ-protective effects and mechanisms of DEX to understand their combined application value.

Figure 1

Main mechanisms of the organ-protective effects of α2AR agonists. α2ARs are classic inhibitory GPCRs (Gi). On the one hand, α2ARs directly inhibit the AC-cAMP-PKA pathway through Gαi proteins; on the other hand, the separation of the Gβγ subunit from Gαi activates the PI3K/Akt pathway and influences a series of downstream signaling including MEK/ERK, HGMB1/TLR4/NF-κB, and IKK/NF-κB. Incidentally, α2AR agonists may inhibit JAK/STAT pathways. But when under high concentrations of an agonist and high receptor expression, α2ARs may couple both physically and functionally to Gs, producing an opposite effect of inhibiting NF-κB.