Moderated Poster

Poster, Podium & Video Sessions

MP42-13: Modulation of nicotinic receptor function by bladder decentralization and reinnervation

Saturday, May 13
3:30 PM - 5:30 PM
Location: BCEC: Room 160

Presentation Authors: Danielle M Salvadeo*, Nagat Frara, Alan S. Braverman, Mary F. Barbe, Michael Ruggieri, Philadelphia, PA

Introduction: We previously found that the depolarizing neuromuscular nicotinic receptor blocker succinylcholine decreased bladder pressure when reinnervated nerves were stimulated. We aim to explore the function and location of nicotinic receptors with respect to loss and recovery of bladder function.

Methods: Three groups of female dogs were used: sham (N=4), 12-month decentralized (N=3) and 6-month reinnervated (N=3). Decentralization was by bilateral transection of spinal roots caudal to L7, including dorsal roots of L7 and hypogastric nerves. The obturator nerve was connected to a bladder branch of the pelvic plexus for reinnervation. At euthanasia, contractile responses of mucosa-free bladder smooth muscle strips were determined.

Results: In reinnervated dogs, IV atracurium, a competitive neuromuscular nicotinic antagonist, decreased bladder pressure induced by transferred obturator nerve stimulation but not sacral nerve root stimulation in shams. Nicotine induced contractions in sham tissue to about 16% of that induced by KCl. ATR blocked nicotine-induced contractions but α,β-ATP did not. 100 μM 1,1 dimethyl-4-phenyl-piperazinium iodide (DMPP), a ganglionic-subtype nicotinic receptor agonist, induced similar contractions in all groups. 10 µM epibatidine (EPB) induced similar contractions in sham and reinnervated animals, but less responses in decentralized animals (p<.05). The α4β2 nicotinic receptor agonist TC2559 had no effect. TTX blocked EFS-induced contractions but not DMPP-, EPB- or nicotine-induced contractions across all groups. ATR and α,β-mATP significantly reduced EFS-evoked contractions in all groups but the competitive neuromuscular nicotinic receptor antagonist d-tubocurarine did not.

Conclusions: While nicotinic receptors mediate contractions in sham, reinnervated and decentralized bladders, pelvic decentralization significantly reduced nicotine-induced effects, suggesting alteration in nicotinic receptor expression. The effects of TTX and atropine on nicotine-induced contractions suggest that nicotinic receptors do not require action potentials to function and are likely located on the presynaptic membrane of cholinergic but not purinergic nerves. The EFS-induced contractions in the presence of d-tubocurarine in the reinnervated bladders indicate that the neuromuscular nicotinic receptors involved in the new neuronal pathway cannot be located in the bladder muscle or intramural ganglia and therefore must be more proximal, perhaps in pelvic plexus ganglia or the spinal cord.

Source Of Funding: NIH-NINDS NS070267

Danielle M. Salvadeo, BS

Lewis Katz School of Medicine at Temple University

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