Detrusor (bladder smooth muscle) contracts via M3 muscarinic activation (parasympathetic, mediates voiding); relaxes via β3-adrenergic (sympathetic, mediates storage). Bladder neck + prostatic urethra contract via α1A-adrenergic (impedes voiding in BPH). Overactive bladder (OAB) Rx blocks the contraction signal: muscarinic antagonists (oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine) or activates the relaxation signal (β3-agonist mirabegron, vibegron). BPH Rx removes urethral resistance: α1-blockers (tamsulosin α1A-selective uroselective; alfuzosin, silodosin uroselective; doxazosin, terazosin non-selective also useful for BP). Long-term BPH: 5α-reductase inhibitors (finasteride, dutasteride — covered in END-1 HPG axis) shrink prostate over months.
Organ Systems
renal
Pathway Steps
detrusor-m3-activation → detrusor-contraction — via parasympathetic ACh → M3/Gq → IP3 → Ca²⁺ → contraction → voiding. The detrusor (bladder wall) muscle contracts to void via parasympathetic acetylcholine acting on M3 muscarinic receptors. This is the target of antimuscarinics (oxybutynin, tolterodine) for overactive bladder — though the same M3 blockade elsewhere causes the dry mouth and constipation that limit them.
detrusor-b3-activation → detrusor-relaxation — via sympathetic NE → β3/Gs → cAMP → relaxation → storage. Detrusor relaxation during filling is promoted by sympathetic β3-adrenergic signaling, letting the bladder store urine at low pressure. The β3 agonist mirabegron exploits this to treat overactive bladder without antimuscarinic side effects — a mechanistically distinct alternative.
urethral-a1a-activation → urethral-contraction — via NE → α1A/Gq → contraction → outlet resistance (BPH urinary obstruction). Continence also requires the internal urethral sphincter to stay contracted, driven by α1A-adrenergic tone. This is why α1-blockers (tamsulosin) relax the bladder outlet to relieve obstruction in BPH — and why they can cause stress incontinence or retrograde ejaculation.
Known Modulators
mirabegron (activator) — β3-adrenergic (detrusor). OAB; relaxation-by-β3 alternative to antimuscarinics; less anticholinergic burden in elderly
terazosin (inhibitor) — α1 (non-selective). BPH + HTN; first-dose syncope; non-uroselective → BP effect more prominent than tamsulosin