BIOCHEMICAL AND FUNCTIONAL CHARACTERISTICS OF BLADDER

MUSCARINIC RECEPTORS AND EFFECTS OF EXPERIMENTAL DIABETES ON THEM IN RATS

Abstract

Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. Voiding function is mainly controlled by muscarinic receptor function. Therefore, I investigated first the biochemical and functional characteristics of urinary bladder muscarinic receptors and then the effects of experimental diabetes on them. Experimental diabetes was induced in 2 month-old male rats by intravenous injection of 65mg/kg of streptozotocin (STZ). Effects of diabetes mellitus were investigated 2, 4 and 8 weeks after injection of STZ. The amount of muscarinic receptors labelled with ³H-quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, while the affinity 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 domes. The rank order of inhibition of ³H-QNB binding by muscarinic agonists and antagonists: bethanechol>pirenzepine>carbamylcholine>acetylcholine>atropine, is consistent with the absence of M1 receptors in the bladder dome. In functional studies muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8 week-old diabetic animal than those from controls. The rank order of ED₅₀s were similar in the control and treated groups, being in good agreement with the Ki values obtained from receptor binding studies. These data show a direct correlation between the diabetes-induced biochemical and functinal alterations in muscarinic receptor properties of the rat bladder.