| Autor: |
Mansfield, Kylie J., Liu, Lu, Mitchelson, Frederick J., Moore, Kate H., Millard, Richard J., Burcher, Elizabeth |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Apr2005, Vol. 144 Issue 8, p1089-1099, 11p |
| Abstrakt: |
We 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.Binding 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).Competition-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.Using RT-PCR, expression of M1, M2, M3 and M5 mRNA was demonstrated in both detrusor and mucosa.The 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.There 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 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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