4.3 Article

Dog and human bladders have different neurogenic and nicotinic responses in inner versus outer detrusor muscle layers

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00084.2022

关键词

axon density and intramural ganglia; bladder wall; epibatidine; muscarinic receptor; nicotinic receptor

资金

  1. National Institute of Neurological Disorders and Stroke of the National Institutes of Health
  2. [R01NS070267]
  3. [R01AG049321]

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This study investigated layer and species variations in detrusor muscle strip responses in dog and human bladders. The results showed differences in receptor expression, distribution, and neurogenic responses between different layers of the bladder muscles, as well as differences in myogenic and muscarinic responses between dogs and humans.
The aim of this study was to investigate layer and species variations in detrusor muscle strip responses to myogenic, neuro-genic, and nicotinic, and muscarinic receptor stimulations. Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips were mounted in muscle baths and maximal responses to neurogenic stimulation using electrical field stimulation (EFS) and myogenic stimulation using potassium chloride (KCl, 120 mM) determined. After washing and re-equilibration was completed, responses to nicotinic re-ceptor agonist epibatidine (10 mu M) were determined followed by responses to EFS and muscarinic receptor agonist bethanechol (30 mu M) in continued presence of epibatidine. Thereafter, strips and full-thickness bladder sections from four additional dogs and three human donors were examined for axonal density and intramural ganglia. In dog bladders, contractions to KCl, epibatidine, and bethanechol were 1.5-to 2-fold higher in the inner longitudinal muscle layer, whereas contractions to EFS were 1.5-fold higher in the outer (both pre-and post-epibatidine). Human bladders showed 1.2-fold greater contractions to epibatidine in the inner layer and to EFS in the outer, yet no layer differences to KCl or bethanechol were noted. In both species, axonal density was 2-to 2.5-fold greater in the outer layer. Dogs had more intramural ganglia in the adventitia/serosa layer, compared with more internal layers and to humans. These findings indicate several layer-dependent differences in receptor expression or distri-bution, and neurogenic responses in dog and human detrusor muscles, and myogenic/muscarinic differences between dog ver-sus humans.

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