Assessment of muscarinic receptor subtypes in human and rat lower urinary tract by tissue segment binding assay.
Muscarinic receptors in the human and rat lower urinary tract (urinary bladder detrusor muscle and mucosa, and prostate) were identified by intact tissue segment binding assays with two radioligands, and the effects of prolonged receptor activation in vitro on muscarinic receptors were examined. Hydrophilic [(3)H]-NMS and hydrophobic [(3)H]-QNB bound to the detrusor muscle segments with the same density, suggesting that the muscarinic receptors were localized at the plasma membrane. While the density of muscarinic receptor was higher in detrusor muscle than in the bladder mucosa and prostate, there was no species-specific difference either in density or in subtype distribution (M(1), M(2), and M(3) subtypes in detrusor; M(2) and M(3) subtypes in bladder mucosa; and M(1) and M(2) subtypes in prostate). Incubation of detrusor strips with carbachol decreased [(3)H]-NMS binding sites within 20 min, followed by a reduction of [(3)H]-QNB binding sites after a 60-min lag phase. The loss of the binding sites over 3 h after carbachol treatment was the same (approximately 40%) for both radioligands. The present intact tissue segment binding assay reveals tissue-specific and plasma membrane distribution of distinct muscarinic receptor subtypes and their dynamic changes (internalization and down-regulation) in lower urinary tract of humans and rats.
Anisuzzaman
Abu Syed Md
AS
Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, School of Medicine, University of Fukui, Eiheiji, Japan.
Morishima
Shigeru
S
Suzuki
Fumiko
F
Tanaka
Takashi
T
Yoshiki
Hatsumi
H
Sathi
Zakia Sultana
ZS
Akino
Hironobu
H
Yokoyama
Osamu
O
Muramatsu
Ikunobu
I
D000368:Aged; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019832:N-Methylscopolamine / Q000378:metabolism; D011467:Prostate / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D019832:N-Methylscopolamine