M(1) and M(3) muscarinic receptors are involved in the release of urinary bladder-derived relaxant factor.
We have investigated the muscarinic receptor subtype(s) mediating the release of urinary bladder-derived relaxant factor that is demonstrated by a coaxial bioassay system. Acetylcholine-induced relaxation of a precontracted anococcygeus muscle mounted within the bladder was considered as an evidence for the release of this factor. M(1)-muscarinic agonist McN-A-343 and the cholinesterase inhibitor physostigmine also elicited relaxation responses in the coaxial bioassay besides acetylcholine. Acetylcholine-induced relaxation was antagonized by the subtype-selective muscarinic antagonists (pK(B)): M(3)-antagonist darifenacin (9.36+/-0.11), M(3)/M(1)-antagonist 4-DAMP (9.30+/-0.11), M(1)-antagonist telenzepine (8.56+/-0.21), M(4)-antagonist tropicamide (6.63+/-0.17) and M(2)-antagonist AF-DX 116 (6.01+/-0.21). The pK(B) values of these antagonists have suggested that stimulation of M(1)- and M(3)-muscarinic receptors in the bladder wall mediates the release of urinary bladder-derived relaxant factor. In addition, McN-A-343, by activating the facilitatory M(1) receptors and physostigmine by inhibiting the acetylcholinesterase may induce the release of this factor through endogenous acetylcholine in the coaxial bioassay system.
Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, 06100 Sihhiye, Ankara, Turkey. turgutb@hacettepe.edu.tr
Turgut Emrah
TE
Bozkurt
Inci
I
Sahin-Erdemli
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D001685:Biological Factors / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D001685:Biological Factors; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D010830:Physostigmine; D000109:Acetylcholine