β3-Adrenoceptors exhibit a restricted expression pattern, particularly in humans. However, they have been found to be upregulated in various cancers and under several conditions associated with hypoperfusion such as congestive heart failure and diabetes for instance in the heart and other tissues. These conditions are frequently associated with hypoxia. Furthermore, direct induction of hypoxia has consistently been reported to cause upregulation of β3-adrenoceptors across various tissues of multiple species including humans, rats, dogs, and fish. While a canonical hypoxia-response element in the promoter of the human β3-adrenoceptor gene may play a role in this, no such sequence was found in rodent homologs. Moreover, not all upregulation of β3-adrenoceptor protein is accompanied by increased expression of corresponding mRNA, indicating that the upregulation may involve factors other than transcriptional changes. We propose that upregulation of β3-adrenoceptors at the mRNA and/or protein level is a general marker of hypoxic conditions. Moreover, it may be an additional pathway whereby cells and tissues adapt to reduced oxygen levels.
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Work in the authors’ labs was supported in part by grants from the Ankara University (15L0237005, 16L0237006, 17L0237002, 17L0230010 to EAI), Deutsche Forschungsgemeinschaft (Mi 294/10-1 to MCM) and TUBITAK (SBAG-115S564 to EAI).
Conflict of interest
MCM is a consultant to Astellas and Velicept related to β3-adrenergic receptors and a shareholder of the latter company. MDM, BAE, and EAI do not report a conflict of interest.
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Dal Monte, M., Evans, B.A., Arioglu-Inan, E. et al. Upregulation of β3-adrenoceptors—a general marker of and protective mechanism against hypoxia?. Naunyn-Schmiedeberg's Arch Pharmacol 393, 141–146 (2020). https://doi.org/10.1007/s00210-019-01780-6
- Congestive heart failure