ABSTRACT
Acetylcholine (Ach) acting on the muscarinic receptors is the major stimulus for the detrusor inducing contraction if the bladder is distended and the bladder volume is at the threshold. There are 5 types muscarinic receptor subtypes cloned (M1-M5). Among them, the M2 subtype distributed dominantly in amount in the detrusor and its role seems to be primarily by blocking stimuli from cAMP-coupled receptors that induce relaxation. In contrast, through M3 receptors on the detrusor the strong contractile stimulus evoked even if its distribution in secondarily common. The excitatory M1 and inhibitory M2 and M4 subtypes are also expresswed prejunctionally. Like detrusor, urothelium also expressed all subtypes of muscarinic receptors, and on stimulation it releases factors affecting bladder afferents and smooth muscle. During inflammation, the expression of muscarinic M5 receptors is increased, particularly in the urothelium, together with a cholinergic-induced production of nitric oxide in the mucosa. This review will be discussed expression and functional effects of muscarinic receptors in the lower urinary tract. Clinical aspects of the different muscarinic receptors and roles in the pathologic conditions included in this discussions.
Subject(s)
Acetylcholine , Clone Cells , Inflammation , Mucous Membrane , Muscle, Smooth , Nitric Oxide , Receptor, Muscarinic M5 , Receptors, Muscarinic , Relaxation , Urinary Bladder , Urinary Tract , UrotheliumABSTRACT
OBJECTIVE@#To observe the expression of Muscarinic receptor M1, M3, M5 subunits in rat flocculus following left unilateral labyrinthectomy (UL).@*METHOD@#The RT-PCR was used to observe the expression of Muscarinic receptor M1, M3, M5 subunits post-unilateral labyrinthectomy and investigate its effect on vestibular compensation.@*RESULT@#Muscarinic receptor M1, M3, M5 subunits were induced decrease in both side flocculus after unilateral labyrinthectomy. The expression was the least in the 1 d flocculus of following UL. The expression is rising from the 3-7 d flocculus of following UL. No difference was observed in the 7 d and sham operation flocculus following UL. No difference was observed in the ipsilateral and contralateral flocculus at any group.@*CONCLUSION@#Muscarinic receptor M1, M3, M5 subunits were induced decrease in the flocculus after unilateral labyrinthectomy. But the significance of the change of Muscarinic receptor M1, M3, M5 subunits in the vestibular compensation is still unknown.
Subject(s)
Animals , Male , Rats , Cerebellum , Metabolism , Functional Laterality , Gene Expression , Postoperative Period , Receptor, Muscarinic M1 , Metabolism , Receptor, Muscarinic M3 , Metabolism , Receptor, Muscarinic M5 , Metabolism , Vestibule, Labyrinth , Metabolism , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of M(5) muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats.</p><p><b>METHODS</b>Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M(5) muscarinic receptor was transferred with the lipofectin.</p><p><b>RESULTS</b>Microinjection of AS-ONs targeting M(5) muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocampus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M(5) muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M(5) muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats.</p><p><b>CONCLUSION</b>Blocking M(5) muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M(5) muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.</p>