Muscarinic Cholinergic Receptors in the Normal and Neurogenic Human Bladder

Abstract

Bladder dysfunction secondary to neurologic conditions occurs in all age groups and is associated with significant morbidity. The role of neuroreceptors in the development of detrusor dysfunction has not been studied previously. Control bladder tissue specimens were obtained from eight children with ureterovesical reflux undergoing ureteral reimplantation and 14 adults with bladder carcinoma undergoing cystectomy. Neurogenic bladder specimens were obtained from 10 children with myelomeningocele and five adults with neurogenic bladder dysfunction undergoing augmentation cystoplasty. Saturation experiments using 3H-N-methylscopolamine (3H-NMS) were performed in these control and neurogenic bladder homogenates. The mean equilibrium dissociation constants in the neurogenic and control bladders were 0.41 nM and 0.55 nM, respectively. The mean density of muscarinic cholinergic (MCh) receptor binding sites in the neurogenic and control bladders was 0.34 fmol/mg wet wt. and 0.65 fmol/mg. wet wt., respectively. Competitive binding experiments with 3H-NMS and various unlabelled MCh antagonists indicated that the pharmacology of MCh binding sites was similar in neurogenic and control bladders. Age was not significantly correlated with MCh receptor density in the control and neurogenic bladders. Muscarinic cholinergic binding sites are homogeneous in neurogenic and control bladders. The lower density of MCh receptors in the neurogenic bladders may represent down regulation of MCh receptors or a replacement of smooth muscle by fibrosis.

A new enzymic method for the isolation and culture of human bladder body smooth muscle cells

“…In spite of the higher abundance of M 2 or m 2 receptors, there is evidence that it is the M 3 subtype that mainly participates in the contraction of the bladder smooth muscle in guinea pigs and humans [Noronha et al, 1991;Caul¢eld, 1993]. In the present study, the binding of [ 3 H]NMS to receptor membrane preparations and to crude membrane fractions from cultured human bladder body smooth muscle cells and human bladder body tissue was inhibited by muscarinic antagonists in a dose-dependent manner, con¢rming the presence of muscarinic receptors.The K d value for human bladder tissue in the present study (0.31nM) was close to that reported by Lepor et al [1989], but the B max value was approximately twice the value of 362 fmol/mg protein reported by these workers. When tissues are used, various components such as ¢broblasts, vascular smooth muscle cells, and endothelial cells may contaminate the bladder smooth muscle cells and decrease the density of receptor binding per milligram of protein.…”

Alpha-1 Blockade Pharmacotherapy in Primitive Psychogenic Premature Ejaculation Resistant to Psychotherapy

“…Some other neurophysiological differences have been found between 'normal' and hypertrophic detrusor mus cles: strong differences in parasympathetic muscarinic receptor ligand affinity has been envisaged [26], a resis tance to atropine-induced contraction emerged [27] and, finally, hypertrophic or denervated detrusor muscle con tractions proved inhibited by calcium antagonists [28], All the above data may mean that the presence or absence of a pharmacological effect on healthy organs may not be fully indicative of the presence or absence of such activity on diseased organs. Placebo activity emerged 1 or 2 days after the onset of treatment and dis appeared immediately upon suspension.…”

Effects of Intravesically Administered Anticholinergics, .BETA.-Adrenergic Stimulant and .ALPHA.-Adrenergic Blocker on Bladder Function in Unanesthetized Rats.

“…The atropine-resistant contraction recognized in the present study was, however, different from that occurring in normal physiological micturition, because RR and BC increased significantly in spite of there being no suppression of MVP. Pharmacologically, three different subtypes of muscarinic receptors (Ml, M2, M3) are distinguished, and M3 is known to be the dominant receptor in the detrusor in humans and rats (Doods et al 1987; Lepor et al 1989;Morita et al 1991). Among the anticholinergics, propantheline and oxybutynin were reported The difference in responses of the rat bladder to atropine and to the other anticholinergics may be due to the difference in selectivity to muscarinic receptor subtypes.…”