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Lookup NU author(s): Jane Eastham, Professor James Gillespie
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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. beta(3)-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 beta(3) agonists has questioned the therapeutic site of action of beta(3) agonists in the bladder. The present study was done to explore the possibility that beta(3)-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 beta(3)-adrenoceptor immuno-reactivity (beta(3)AR-IR). The only structures found to express beta(3)AR-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 beta(3)AR-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 beta(3)-adrenoceptor agonists is to modulate sensation, it is possible that these neural circuits may be involved in the regulation of afferent outflow and sensation.
Author(s): Eastham J, Stephenson C, Korstanje K, Gillespie JI
Publication type: Article
Publication status: Published
Journal: Naunyn-Schmiedeberg's Archives of Pharmacology
Year: 2015
Volume: 388
Issue: 7
Pages: 695-708
Print publication date: 01/07/2015
Online publication date: 29/04/2015
Acceptance date: 31/03/2015
ISSN (print): 0028-1298
ISSN (electronic): 1432-1912
Publisher: Springer
URL: http://dx.doi.org/10.1007/s00210-015-1122-5
DOI: 10.1007/s00210-015-1122-5
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