Muscarinic cholinergic receptor subtypes in human detrusor muscle studied by labeled and nonlabeled pirenzepine, AFDX-116 and 4DAMP.
The densities of M1, M2 and M3 muscarinic receptors in human detrusor muscle were measured using 3H-pirenzepine (3H-PZP), 3H-AFDX-116 (3H-AFDX) and 3H-4-diphenyl-acetoxy-N-methyl-piperidine methidide (3H-4DAMP). The affinities of PZP, AFDX and 4DAMP for human detrusor were determined in inhibition experiments with 3H-quinuclidinyl benzilate (3H-QNB). Saturation experiments with 3H-PZP, 3H-AFDX and 3H-4DAMP revealed the presence of M1, M2 and M3 receptors in human detrusor. The KD values (nM) and the Bmax values (fmol/mg protein) (mean +/- SD, n = 6) were 0.84 +/- 0.15 and 13.04 +/- 1.54 for 3H-PZP, 0.68 +/- 0.21 and 9.30 +/- 1.10 for 3H-AFDX, and 0.25 +/- 0.13 and 102.1 +/- 7.40 for 3H-4DAMP. These data indicate that the bladder muscarinic receptors consist mainly of the M3 subtype. Nonlabeled PZP, AFDX and 4DAMP inhibited the 3H-QNB binding to human detrusor with Ki values (nM) (mean +/- SD, n = 6) of 243 +/- 62.5, 59.7 +/- 15.3, 2.69 +/- 0.96, respectively. Human detrusor was found to have a high affinity for 4DAMP. These data suggest that M3 muscarinic receptors are biochemically predominant in human detrusor muscle.
Kondo
S
S
Second Department of Biochemistry, Akita University School of Medicine, Japan.
Morita
T
T
Tashima
Y
Y
D000368:Aged; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000601:surgery
D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C048593:otenzepad