ADRA2B, encoding the α2B adrenoceptor, plays a role in the regulation of norepinephrine availability. It belongs to the GPCR family and is part of the biogenic amine receptors sub-cluster. Through interacting with ligands like l-adrenaline, it can impact cAMP-related pathways, which are intricately involved in various biological processes, such as the regulation of immune responses [1,5].

Research on ADRA2B has revealed several significant findings. Carriers of the ADRA2B Glu(301)-Glu(303) deletion variant show enhanced emotional memory, greater amygdala responses to emotional stimuli, and greater intrusiveness of traumatic memories. In addition, this deletion variant may selectively predict stress-induced enhancement of long-term memory in females [2]. Stress administered immediately before learning selectively enhances long-term recall in deletion carriers, while stress 30 min before learning has different effects on male and female deletion carriers, impairing recognition memory in males but enhancing it in females [3]. Genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus, with deletion carriers showing different neural activity patterns in the amygdala under stress compared to non-carriers [4]. Moreover, l-adrenaline acting on ADRA2B can inhibit the activation of the caspase-11 inflammasome, blocking interleukin-1β maturation, gasdermin D cleavage, and DAMP release, protecting against LPS-induced lethality in poly(I:C)-primed mice [5].

In conclusion, ADRA2B is crucial in the regulation of emotional memory and stress-related memory processes, with its deletion variant showing sex-specific effects. It also plays a role in the immune regulation against sepsis through the cAMP-related pathway. The study of ADRA2B, especially through the analysis of its deletion variant as a form of functional study, helps to understand the mechanisms underlying stress-related psychological disorders and immune-related diseases [2,3,4,5].

References:

1. Papageorgiou, Louis, Christou, Evangelia, Louka, Effrosyni, Eliopoulos, Elias, Vlachakis, Dimitrios. . ADRA2B and HTR1A: An Updated Study of the Biogenic Amine Receptors Reveals Novel Conserved Motifs Which Play Key Role in Mental Disorders. In Advances in experimental medicine and biology, 1423, 79-99. doi:10.1007/978-3-031-31978-5_7. https://pubmed.ncbi.nlm.nih.gov/37525034/

2. Zoladz, Phillip R, Kalchik, Andrea E, Hoffman, Mackenzie M, Talbot, Jeffery N, Rorabaugh, Boyd R. 2014. ADRA2B deletion variant selectively predicts stress-induced enhancement of long-term memory in females. In Psychoneuroendocrinology, 48, 111-22. doi:10.1016/j.psyneuen.2014.06.012. https://pubmed.ncbi.nlm.nih.gov/24997351/

3. Zoladz, Phillip R, Dailey, Alison M, Nagle, Hannah E, Earley, McKenna B, Rorabaugh, Boyd R. 2017. ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory. In Neurobiology of learning and memory, 140, 71-81. doi:10.1016/j.nlm.2017.02.014. https://pubmed.ncbi.nlm.nih.gov/28254464/

4. Li, Shijia, Weerda, Riklef, Milde, Christopher, Wolf, Oliver T, Thiel, Christiane M. 2014. ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval. In Psychopharmacology, 232, 755-64. doi:10.1007/s00213-014-3710-3. https://pubmed.ncbi.nlm.nih.gov/25127926/

5. Chen, Ruochan, Zeng, Ling, Zhu, Shan, Tang, Daolin, Kang, Rui. 2019. cAMP metabolism controls caspase-11 inflammasome activation and pyroptosis in sepsis. In Science advances, 5, eaav5562. doi:10.1126/sciadv.aav5562. https://pubmed.ncbi.nlm.nih.gov/31131320/