Muscarinic cholinergic receptors in normal pediatric and myelodysplastic bladders

Radioligand receptor binding experiments and in vitro muscle contractile studies were performed to determine the binding and functional properties of detrusor muscarinic cholinergic receptors in control and myelodysplastic bladders. Control bladder tissue was obtained from 8 children with primary vesicoureteral reflux undergoing ureteral reimplantation and 1 child at the time of organ transplant harvesting. Bladder specimens also were obtained from 10 children with myelomeningocele undergoing augmentation cystoplasty. Preoperative cystograms revealed that all children with vesicoureteral reflux had a smooth-walled bladder with normal capacity, whereas those with myelomeningocele undergoing augmentation cystoplasty had a small capacity bladder with trabeculations. Experiments were performed on detrusor tissue obtained from the bladder body in all cases. Radioligand receptor binding experiments with the 3H-N-methylscopolamine revealed that the equilibrium dissociation constant in control and myelodysplastic bladders was 0.44 +/- 0.09 and 0.40 +/- 0.10 nM., respectively. The equilibrium dissociation constant was similar in control and myelodysplastic bladders. The muscarinic cholinergic receptor density (Bmax) in control and myelodysplastic bladders was 0.66 +/- 0.12 and 0.24 +/- 0.03 fmol. per micrograms, protein, respectively. The significantly lower density of muscarinic cholinergic receptors in the myelodysplastic bladders may be explained by either a down regulations or by the histologically observed development of fibrosis. Concentration response experiments were performed on 7 control and 6 myelodysplastic bladders using carbachol and potassium chloride. The carbachol and potassium chloride concentrations producing half of the maximal response were similar in the control and myelodysplastic bladders, suggesting that detrusor dysfunction in myelodysplasia is not associated with detrusor supersensitivity. The maximal response (Emax) for potassium chloride was less in the myelodysplastic bladders than in the control bladders but the carbachol Emax was not significantly different. Concentration inhibitory experiments with oxybutynin and imipramine demonstrated that the myelodysplastic and control bladders were identically inhibited by these antagonists. Radioligand receptor binding studies and in vitro contractile experiments indicate that the detrusor dysfunction associated with myelomeningocele is not mediated by changes in the binding or functional properties of detrusor muscarinic cholinergic receptors.