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논문 기본 정보

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학술저널
저자정보
Darryl Kitney (School of Physiology Pharmacology and Neuroscience University of Bristol) John Crook (School of Physiology Pharmacology and Neuroscience University of Bristol) Basu Chakrabarty (School of Physiology Pharmacology and Neuroscience University of Bristol) Anthony Kanai (School of Medicine University of Pittsburgh) Bahareh Vahabi (Department of Applied Sciences University of the West of England) Thelma Lovick (School of Physiology Pharmacology and Neuroscience University of Bristol) Christopher Fry (School of Physiology Pharmacology and Neuroscience University of Bristol)
저널정보
대한배뇨장애요실금학회 International Neurourology Journal International Neurourology Journal 제25권 제3호
발행연도
2021.9
수록면
210 - 218 (9page)
DOI
10.5213/inj.2142002.001

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Purpose: The urinary bladder generates phasic contractions via action potentials generated in pre- and then postganglionic neurons. Whilst the frequency-dependence of postganglionic neurons to generate contractions has been quantified, the dynamic range of preganglionic neurons is less clear and if intramural ganglia exert frequency-dependent modulation of transmission between pre- and postganglionic neurons. The phosphodiesterase type 5 inhibitor sildenafil reduces neurotransmitter release from postganglionic fibres to detrusor smooth muscle and an additional question was if there was also a preganglionic action. This study aimed to compare the frequency range of bladder contractile activation by pre- and postganglionic stimulation in pig and rat bladders and if sildenafil exerted additional preganglionic actions. Methods: An arterially-perfused ex vivo pig bladder preparation was used for preganglionic (pelvic nerve) and mixed preand postganglionic (direct bladder wall) stimulation at 36°C and postganglionic mediated contractions achieved by field-stimulation of in vitro isolated detrusor strips. With rats, pelvic nerve stimulation was carried out in vivo and postganglionic stimulation also with isolated detrusor strips. Results: All contractions were abolished by 2% lignocaine indicating they are nerve-mediated. Stimulation targets were verified with hexamethonium that completely abolished pelvic nerve responses by had no effect on detrusor strips; responses to mixed bladder wall stimulation were partially reduced. The frequency-dependence of contractile activation was similar whether by pre- or postganglionic stimulation in both pigs and rats. Sildenafil reduced contractions to preganglionic stimulation significantly more than to postganglionic stimulation. Mixed pre- and postganglionic stimulation were reduced by an intermediate extent. Conclusions: Intramural ganglia offer no frequency-dependent modulation under the experimental conditions used here and the sildenafil data are consistent with multiple sites of action underlying generation of bladder contractions. A translational aspect of these findings is discussed in terms of setting stimulation parameters for neuromodulation protocols.
#Bladder #Pelvic nerve #Nerve-mediated contractions #Sildenafil #Hexamethonium

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참고문헌 (23)

참고문헌 신청
de Groat WC / 1976 / Synaptic transmission in parasympathetic ganglia in the urinary bladder of the cat / J Physiol 256:137~158 google schola de Groat WC / 1981 / Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine / J Auton Nerv Syst 3:135~160 google schola Moffatt JD / 1999 / Characterization of non‐adrenergic, non‐cholinergic inhibitory responses of the isolated guinea‐pig trachea: differences between pre‐ and post‐ganglionic nerve stimulation / Br J Pharmacol 128:459~464 google schola Rimmer K / 2010 / Weak and straddling secondary nicotinic synapses can drive firing in rat sympathetic neurons and thereby contribute to ganglionic amplification / Front Neurosci 1:130 google schola Chakrabarty B / 2019 / Influence of sildenafil on the purinergic components of nerve-mediated and urothelial ATP release from the bladder of normal and spinal cord injured mice / Br J Pharmacol 176:2227~2237 google schola

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