Effects of experimental diabetes on biochemical and functional characteristics of bladder muscarinic receptors.

Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. We investigated the effects of experimental diabetes on muscarinic receptors in rat bladder smooth muscle, 2, 4 and 8 weeks after i.v. injection of 65 mg/kg of streptozotocin. At all time points, diabetic animals had a lower body weight, higher serum glucose levels and reduced serum insulin levels than age-matched controls. Diabetic animals had a markedly increased urine output and significant enlargement of the bladder dome. The amount of muscarinic receptor labeled with [3H]quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, whereas the affinity of the labeled antagonist for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited [3H]QNB binding with similar inhibitory constants (Ki) in control and diabetic dome. The rank order of Ki values in inhibition of [3H]QNB binding by muscarinic agonists and antagonists: atropine less than acetylcholine less than carbachol less than AF-DX 116 = pirenzepine less than bethanechol, is consistent with the presence of M2 muscarinic receptors in the bladder dome. In functional studies, muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8-week-diabetic animals than from controls. ED50 values were similar in control and treated groups, with the rank order of ED50 values being in good agreement with the Ki values obtained from receptor binding studies, i.e., acetylcholine less than carbachol less than bethanechol. These data show a direct correlation between the diabetes-induced biochemical and functional alterations in muscarinic receptor properties of rat bladder.