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The expression of β3-adrenoceptor and muscarinic type 3 receptor immuno-reactivity in the major pelvic ganglion of the rat

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Abstract

Bladder afferent outflow, linked to sensation, plays a critical role in bladder pathology: abnormal outflow results in altered sensation, leading to increased voiding frequency, urge and often incontinence. β3-adrenoceptor agonists have been suggested to be beneficial in treating these symptoms. However, the absence of a significant sympathetic innervation of the detrusor and only a modest relaxation of bladder muscle by β3 agonists has questioned the therapeutic site of action of β3 agonists in the bladder. The present study was done to explore the possibility that β3-adrenoceptors might be located in the pelvic plexus. Using the rat, where the pelvic plexus is located primarily within a single ganglion, the major pelvic ganglion (MPG), immuno-histochemical approaches were used to identify structures expressing β3-adrenoceptor immuno-reactivity (β3AR-IR). The only structures found to express β3AR-IR were small-diameter tyrosine hydroxylase and vesicular mono-amine transporter immuno-reactive (TH-IR and vmat-IR) neurones. These neurones, found in clusters or singly on the periphery of the ganglion, or dispersed in smaller clumps throughout the MPG, are similar to the small intensely fluorescent (SIF) cells described previously. Not all small cells expressed β3AR-IR. A population of the small cells were also immuno-reactive to the type 3 muscarinic receptor (M3R-IR) and the P2X3 purinergic receptor (P2X3-IR). Clumps of small cells were associated with calcitonin gene-related peptide immuno-reactive (CGRP-IR) nerve fibres (putative sensory fibres) and a small number were contacted by putative cholinergic nerves expressing immuno-reactivity to vesicular acetylcholine transporter (vacht-IR). These observations are consistent with the idea that small cells are interneurons and one of the components making up complex neural circuits within the MPG. The precise physiological role of these neural elements in the MPG is unknown. However, as one therapeutic action of β3-adrenoceptor agonists is to modulate sensation, it is possible that these neural circuits may be involved in the regulation of afferent outflow and sensation.

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This manuscript has been prepared to comply with all required ethical standards. There are no conflicts of interest to be declared.

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Authors and Affiliations

  1. Uro-physiology Research Group, The Dental and Medical School, Newcastle University, Newcastle Upon Tyne, NE2 4HH, England, UK

    J. Eastham, C. Stephenson & J. I. Gillespie

  2. Astellas Pharma Europe B.V., Elisabethhof 1, 2353 EW, Leiderdorp, The Netherlands

    K. Korstanje

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  1. J. Eastham
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  2. C. Stephenson
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  4. J. I. Gillespie
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Correspondence to J. I. Gillespie.

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Eastham, J., Stephenson, C., Korstanje, K. et al. The expression of β3-adrenoceptor and muscarinic type 3 receptor immuno-reactivity in the major pelvic ganglion of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 388, 695–708 (2015). https://doi.org/10.1007/s00210-015-1122-5

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