The M₃-Muscarinic Cholinoceptor Subtype in Rat Prostate and Its Down Regulation by Aging

抄録

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 (K_D value)of 0.24 ± 0.04 nM and a maximum binding site number (B_max)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 > [1 l-((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, B_max 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, K_D values for muscarinic cholinoceptors, and B_max and K_D values for β-adrenoceptors showed no change. These results suggest that the number of prostatic muscarinic cholinoceptors decreases with aging.