- 1We investigated muscarinic receptors in the detrusor and mucosa of the human bladder body. Radioligand-binding studies with [3H]QNB were conducted using specimens collected from patients (36–77 years) with normal bladder function, undergoing surgery. For RT–PCR, biopsies of normal bladder were obtained from patients (30–88 years) undergoing check cystoscopy.
- 2Binding of [3H]QNB in detrusor (n=20) was of high affinity (KD 77.1 (55.2–99.0) pM) and capacity (Bmax 181±7 fmol mg protein−1). Similar values were obtained in mucosa (n=6) (KD 100.5 (41.2–159.9) pM; Bmax 145±9 fmol mg protein−1).
- 3Competition-binding experiments in detrusor membranes with muscarinic receptor antagonists including trospium, darifenacin, 4-DAMP, methoctramine, AQ-RA 741, AF-DX 116 and pirenzepine indicated a receptor population of 71% M2, 22% M3 and 7% M1. In the mucosa, 75% of sites were M2 receptors, with 25% M3/M5.
- 4Using RT–PCR, expression of M1, M2, M3 and M5 mRNA was demonstrated in both detrusor and mucosa.
- 5The presence of a high density of mainly M2 muscarinic receptors in the mucosa appears to be a novel finding and raises the question of their physiological significance and the source of their endogenous ligand.
- 6There was a negative correlation of receptor number (Bmax) with age in detrusor muscle from male patients (P=0.02). Quantitative competitive RT–PCR demonstrated a selective age-related decrease in mRNA for muscarinic M3 but not M2 receptors, in both male (P<0.0001) and female (P=0.019) detrusor. These findings correspond with reports of decreased detrusor contractility with ageing.
British Journal of Pharmacology (2005) 144, 1089–1099. doi:10.1038/sj.bjp.0706147