Effect of age on cholinergic muscarinic responsiveness and receptors in the rat urinary bladder

The effects of age on urinary bladder responsiveness to muscarinic agonists and on the Bmax and Kd of the binding of [3H]quinuclidinyl benzilate (QNB) to muscarinic receptors of the bladder were studied. Bladder bodies and bases were isolated from Fischer 344 rats, ages seven, 16 and 27 months. No age-dependent change in maximum KCl-elicited isotonic contractions was observed in either bladder region. The bladder base showed an age-dependent increase in the maximum contractions (Emax) elicited by muscarinic agonists. The Emax values for bladder bases from rats 27 months of age were 44 per cent, 58 per cent and 76 per cent greater than those from rats seven months of age for acetylcholine, bethanechol and oxotremorine, respectively. No such alteration in responsiveness was observed in the bladder body with age. There were no age-related changes in ED50 values for the three agonists in either bladder region. Analysis of [3H]QNB binding in the bladder base demonstrated a modest 18 per cent increase in the Bmax (fmol./mg. tissue) from seven to 16 months and a significant 39 per cent decrease from 16 to 27 months. In the bladder body, the Bmax progressively increased by 25 per cent from seven to 27 months. The Kd values of [3H]QNB did not change with age in either region. The data demonstrate that the age-related increase in the responsiveness of the bladder is regionally specific and cannot be explained by a change in the number or affinity of muscarinic receptors.