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Effects of cholinesterase inhibition in supraspinal and spinal neural pathways on the micturition reflex in rats
Author(s) -
Masuda Hitoshi,
Chancellor Michel B.,
Kihara Kazunori,
Sakai Yasuyuki,
Koga Fumitaka,
Azuma Hiroshi,
De Groat William C.,
Yoshimura Naoki
Publication year - 2009
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2009.08515.x
Subject(s) - methoctramine , neostigmine , pirenzepine , muscarinic acetylcholine receptor , atropine , antagonist , muscarinic antagonist , chemistry , mecamylamine , pharmacology , anesthesia , endocrinology , medicine , receptor
OBJECTIVE To investigate whether activation of brain and spinal cholinergic pathways affects the micturition reflex in rats. MATERIALS AND METHODS The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of neostigmine as a cholinesterase inhibitor and oxotremorine‐M (OXO‐M) as a muscarinic acetylcholine receptor (mAChRs) agonist, on the micturition reflex were evaluated by infusion cystometrography (CMG) in urethane‐anaesthetized untreated rats or rats pretreated with capsaicin. RESULTS Neostigmine injected i.c.v. increased bladder capacity (BC) and pressure threshold (PT) dose‐dependently, with an increase in maximum voiding pressure (MVP) and a decrease in voiding efficiency (VE) at higher doses. Also, neostigmine injected i.t. increased the BC and PT dose‐dependently without changing MVP or VE, and these effects were not apparent in capsaicin‐pretreated rats. In both routes, atropine as an antagonist of mAChRs, but not mecamylamine as a nicotinic‐AChR antagonist, almost completely antagonized the effects of neostigmine. The rank order of potencies of the antagonists for increasing effects of BC induced by 1 nmol of neostigmine was: pirenzepine (an M 1 mAChR antagonist) = atropine > 4‐DAMP (an M 3 mAChR antagonist) >> methoctramine (an M 2 mAChR antagonist) and tropicamide (an M 4 mAChR antagonist) via the i.c.v. route; and atropine > methoctramine > pirenzepine > tropicamide and 4‐DAMP via the i.t. route, respectively. OXO‐M injected via i.c.v. and i.t. had the same effects on BC, PT, MVP and VE as neostigmine by i.c.v. and i.t., respectively. CONCLUSIONS These results indicate that activation of muscarinic cholinergic mechanisms by the cholinesterase inhibitor in the brain and spinal cord can inhibit the micturition reflex, mainly by affecting afferent pathways. These mAChR‐induced inhibitory effects seem to be mediated through M 1 /M 3 receptor subtypes in the brain, while in the spinal cord, the M 1 /M 2 receptor subtypes might be involved in inhibitory effects, which are mediated via inhibition of mechanoceptive C‐fibre afferent pathways.