[Changes in the receptor profile of the aging bladder]

Future demographic developments will challenge urology with a steadily increasing incidence of lower urinary tract symptoms (LUTS) derived from the aging bladder. Obstruction, instability and hypocontractility, which may be caused by changes in the receptor profile of the detrusor, are typical pathophysiologic findings in geriatric bladder dysfunction. Benign prostatic hyperplasia and diabetes mellitus are age-associated comorbidities with an additional influence on bladder receptors. Muscarinic (M(2), M(3)), purinergic (P2X, P2Y) and adrenergic receptors (alpha(1), beta(3)) are targets of efferent sympathetic and parasympathetic bladder innervation. Although the results from animal experiments are somewhat inconsistent, aging and bladder outlet obstruction (BOO) probably cause partial cholinergic denervation of the detrusor with a subsequent upregulation of muscarinic receptor sensitivity leading to bladder instability. The non-cholinergic (atropine-resistant) component of the detrusor contraction rises with aging and BOO to 50%, emphasizing the increasing impact of purinergic receptors in geriatric LUTS. alpha(1)-adrenergic receptors are modulated in the aging bladder by a shift from the predominant alpha(1a) subtype to the alpha(1d) subtype, which shows 100-fold higher affinity towards norepinephrine and increases alpha-adrenergic bladder susceptibility. No data are available on the changes in beta(3) receptor density or sensitivity with aging. Moreover, the role of sensory C-fiber receptors in geriatric LUTS remains completely unclear, although specific C-fiber blockers are already under clinical evaluation (capsaicin, resiniferatoxin).