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  • Title: The M3-muscarinic cholinoceptor subtype in rat prostate and its down regulation by aging.
    Author: Yazawa H, Honda K.
    Journal: Jpn J Pharmacol; 1993 Apr; 61(4):319-24. PubMed ID: 8320877.
    Abstract:
    Muscarinic cholinoceptor subtypes in the rat prostatic membrane were characterized by using [3H]-methyl-quinuclidinyl benzilate (QNB) in ligand binding studies. [3H]-Methyl-QNB saturation experiments showed the existence of a homogeneous population of binding sites with a high affinity (KD value) of 0.24 +/- 0.04 nM and a maximum binding site number (Bmax) of 219 +/- 65 fmol/mg protein. Inhibition of [3H]-methyl-QNB binding by nonlabelled compounds was in the following order of effectiveness in rat prostate: atropine > 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > hexahydro-sila-difenidol hydrochloride, p-fluoroanalog (p-F-HHSiD) > pirenzepine > methoctramine > [11-((2-((dimethylamino)-methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6H- pyrido(2,3-b)(1,4)benzodiazepine-6-one] (AF-DX 116). This ranking order was similar to that for the salivary gland (M3 subtype), but not for the brain (M1 subtype) or the heart (M2 subtype). These results indicate that the muscarinic cholinoceptors in the rat prostate belong mainly to the M3 subtype. Furthermore, Bmax values for muscarinic cholinoceptors in the aged rat prostate (approximately 1-year-old) were smaller than those in the young rat prostate (6- to 8-week-old) (87 +/- 13 vs. 183 +/- 32 fmol/mg protein). However, KD values for muscarinic cholinoceptors, and Bmax and KD values for beta-adrenoceptors showed no change. These results suggest that the number of prostatic muscarinic cholinoceptors decreases with aging.
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