Tissue functions mediated by β3-adrenoceptors—findings and challenges

Abstract

As β3-adrenoceptor agonists metamorphose from experimental tools into therapeutic drugs, it is vital to obtain a comprehensive picture of the cell and tissue functions mediated by this receptor subtype in humans. Human tissues with proven functions and/or a high expression of β3-adrenoceptors include the urinary bladder, the gall bladder, and other parts of the gastrointestinal tract. While several other β3-adrenoceptor functions have been proposed based on results obtained in animals, their relevance to humans remains uncertain. For instance, β3-adrenoceptors perform an important role in thermogenesis and lipolysis in rodent brown and white adipose tissue, respectively, but their role in humans appears less significant. Moreover, the use of tools such as the agonist BRL 37344 and the antagonist SR59230A to demonstrate functional involvement of β3-adrenoceptors may lead in many cases to misleading conclusions as they can also interact with other β-adrenoceptor subtypes or even non-adrenoceptor targets. In conclusion, we propose that many responses attributed to β3-adrenoceptor stimulation may need re-evaluation in the light of the development of more selective tools. Moreover, findings in experimental animals need to be extended to humans in order to better understand the potential additional indications and side effects of the β3-adrenoceptor agonists that are beginning to enter clinical medicine.

Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

“…Studies on rat DSM have shown that BRL37744 also exhibit some antimuscarinic properties (5,26,30). In our study, we addressed this issue by using the muscarinic receptor antagonist atropine.…”

Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease

“…The b 3 -adrenoceptor was originally assigned a role in promoting lipolysis and thermogenesis (Emorine et al, 1989;Arch, 2008), yet this function is most likely restricted to rodents (Michel et al, 2010). Multiple other roles for the b 3 -adrenoceptor were subsequently elucidated, including activation of nitric oxide synthase in cardiomyocytes, relaxation of the urinary bladder (Michel et al, 2010), and most recently release of hematopoietic stem cells and progenitor cells from the bone marrow in myocardial infarction (Dutta et al, 2012). The b 3 -subtype was the last of the b-adrenoceptors to Ahles and Engelhardt be cloned and has been studied considerably less compared with the b 1 -and the b 2 -subtype.…”

The Odd Sibling: Features of β3-Adrenoceptor Pharmacology

“…Therefore, most tissue mapping has relied on functional studies. Although this has provided robust evidence for a dominant role of the b 3 subtype in human bladder smooth muscle relaxation (Michel and Vrydag, 2006), the evidence for involvement of this subtype in the regulation of other tissues is less convincing due to a limited number of studies and poor selectivity of many of the tools used in those studies (Michel et al, 2010).…”