¹Department of Pharmacology & Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

Correspondence: Martin C. Michel, Department of Pharmacology & Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail: m.c.michel@amc.uva.nl

Abstract

1. We have systematically reviewed the presence, functional responses and regulation of ₁-, ₂- and -adrenoceptors in the bladder, urethra and prostate, with special emphasis on human tissues and receptor subtypes.
2. ₁-Adrenoceptors are only poorly expressed and play a limited functional role in the detrusor. ₁-Adrenoceptors, particularly their _1A-subtype, show a more pronounced expression and promote contraction of the bladder neck, urethra and prostate to enhance bladder outlet resistance, particularly in elderly men with enlarged prostates. ₁-Adrenoceptor agonists are important in the treatment of symptoms of benign prostatic hyperplasia, but their beneficial effects may involve receptors within and outside the prostate.
3. ₂-Adrenoceptors, mainly their _2A-subtype, are expressed in bladder, urethra and prostate. They mediate pre-junctional inhibition of neurotransmitter release and also a weak contractile effect in the urethra of some species, but not humans. Their overall post-junctional function in the lower urinary tract remains largely unclear.
4. -Adrenoceptors mediate relaxation of smooth muscle in the bladder, urethra and prostate. The available tools have limited the unequivocal identification of receptor subtypes at the protein and functional levels, but it appears that the ₃- and ₂-subtypes are important in the human bladder and urethra, respectively. ₃-Adrenoceptor agonists are promising drug candidates for the treatment of the overactive bladder.
5. We propose that the overall function of adrenoceptors in the lower urinary tract is to promote urinary continence. Further elucidation of the functional roles of their subtypes will help a better understanding of voiding dysfunction and its treatment.