Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 393, Issue 2, pp 141–146 | Cite as

Upregulation of β3-adrenoceptors—a general marker of and protective mechanism against hypoxia?

  • Massimo Dal Monte
  • Bronwyn A. Evans
  • Ebru Arioglu-Inan
  • Martin C. MichelEmail author


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.


β3-Adrenoceptor Upregulation Hypoxia Cancer Congestive heart failure Diabetes 


Author contribution

MDM, EAI, and MCM conceived the project. MDM and EAI performed the literature search for cancer and cardiovascular disease, respectively. BAE performed the gene promoter analysis. MCM drafted the manuscript. All the authors read, critically revised, and approved the manuscript.

Funding information

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).

Compliance with ethical standards

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiologyUniversity of PisaPisaItaly
  2. 2.Drug Discovery Biology, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia
  3. 3.Department. of Pharmacology, Faculty of PharmacyAnkara UniversityAnkaraTurkey
  4. 4.Department. of PharmacologyJohannes Gutenberg UniversityMainzGermany

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