Beta-3 adrenergic receptor

Function

Actions of the β3 receptor include

• Enhancement of lipolysis in adipose tissue.
• Thermogenesis in skeletal muscle

It is located mainly in adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Some β3 agonists have demonstrated antistress effects in animal studies, suggesting it also has a role in the central nervous system (CNS). β3 receptors are found in the gallbladder, urinary bladder, and in brown adipose tissue. Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown fat. In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination.

Mechanism of action

Beta adrenergic receptors are involved in the epinephrine- and norepinephrine-induced activation of adenylate cyclase through the action of the G proteins of the type Gs.

Ligands

Agonists

Approved for clinical use

• Mirabegron (YM-178), approved for treatment of overactive bladder in Japan, United States, UK, Canada, China and India.
• Nebivolol selective beta(1)-blocker and beta(3)-agonist.
• Vibegron (MK-4618)

Experimental

• Amibegron (SR-58611A)
• BRL-37344
• CL-316,243
• L-742,791
• L-796,568
• LY-368,842
• Ro40-2148
• Solabegron (GW-427,353)

Antagonists

• L-748,328
• L-748,337
• SR 59230A was thought to be a selective β3 antagonist but later found to also be an antagonist of the α1 receptor.

Interactions

Beta-3 adrenergic receptor has been shown to interact with Src.

References

References

1. "Entrez Gene: ADRB3 adrenergic, beta-3-, receptor".
2. (September 2005). "Combined effects of oleoyl-estrone and a β₃-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats". Life Sciences.
3. Rang, H. P.. (2003). "Pharmacology". Churchill Livingstone.
4. (2006). "Recent Developments in the Design of Orally Bioavailable β3-Adrenergic Receptor Agonists". Current Medicinal Chemistry.
5. (2012). "Mirabegron for the treatment of overactive bladder". Drugs of Today.
6. (2009). "Nebivolol, a vasodilating selective beta(1)-blocker, is a beta(3)-adrenoceptor agonist in the nonfailing transplanted human heart". J Am Coll Cardiol.
7. (January 2016). "Discovery of Vibegron: A Potent and Selective β3 Adrenergic Receptor Agonist for the Treatment of Overactive Bladder.". Journal of Medicinal Chemistry.
8. (November 2007). "Behavioral effects of the β₃ adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant/anxiolytic drugs?". European Journal of Pharmacology.
9. (June 2008). "Confirmation of antidepressant potential of the selective β₃ adrenoceptor agonist amibegron in an animal model of depression". Pharmacology Biochemistry and Behavior.
10. (May 2019). "BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via β2-adrenoceptors without causing classical receptor desensitization". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology.
11. (2008). "The effects of beta(3)-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-alpha expressions in adipose tissues of obese diabetic KKAy mice". European Journal of Pharmacology.
12. (Aug 1999). "Potent and selective human beta(3)-adrenergic receptor antagonists.". The Journal of Pharmacology and Experimental Therapeutics.
13. (2002). "Effect of a 28-d treatment with L-796568, a novel β₃-adrenergic receptor agonist, on energy expenditure and body composition in obese men". The American Journal of Clinical Nutrition.
14. (October 2007). "GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog". The Journal of Pharmacology and Experimental Therapeutics.
15. (1996). "Functional studies of the first selective β₃-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Mol. Pharmacol..
16. (April 2009). "Role of α1- and β3-adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouse". British Journal of Pharmacology.
17. (2000). "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem..