Topographic distribution of serotonin-immunoreactive urethral endocrine cells and their relationship with calcitonin gene-related peptide-immunoreactive nerves in male rats

Yokoyama, Takuya; Saino, Tomoyuki; Nakamuta, Nobuaki; Yamamoto, Yoshio

doi:10.1016/j.acthis.2016.11.011

Cited by 11 publications

(22 citation statements)

References 26 publications

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“…). In contrast, in the male rat, 5‐HT + cells were densely distributed in the prostatic urethra, but sparsely distributed in the membranous and spongy parts of the urethra . Together, these distinct morphological features and anatomical locations suggest that different classes of 5‐HT + cells may detect different stimuli and likely serve different functions, which could differ based on sex.…”

Section: Discussionmentioning

confidence: 87%

“…Previous studies investigated 5‐HT + cells in the urethra of different species using transverse sections . It is now clear that this methodology underestimates the morphological complexity of these cells as well as their relationships with each other and with nerve fibres; these characteristics are better captured using whole‐mount preparations and confocal microscopy.…”

Section: Discussionmentioning

confidence: 99%

“…The urethral epithelium is composed of several layers of cells forming an interface between the lumen and the underlying nervous, vasculature, connective and muscular tissues . Besides epithelial cells, this epithelium contains other populations of cells, collectively called paraneurones (also named neuroendocrine, chemosensory or brush‐like cells), identified by their transmitter content, including acetylcholine (ACh), serotonin (5‐HT) or somatostatin . Morphologically, some paraneurones are described as possessing dendrite‐like processes spanning the epithelium, while others have an apical tuft of microvilli at the luminal surface of the urethra.…”

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confidence: 99%

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Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing

et al. 2017

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Aim The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here, we examined the morphology and potential role in sensory signalling of a different class of specialized cells that express serotonin (5-HT), termed paraneurones. Methods Urethrae, dorsal root ganglia neurones and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging. Visceromotor reflexes (VMRs) were recorded in vivo. Results We identified two morphologically distinct groups of 5-HT+ cells with distinct regional locations: bipolar-like cells predominant in the mid-urethra and multipolar-like cells predominant in the proximal and distal urethra. Sensory nerve fibres positive for calcitonin gene-related peptide, substance P, and TRPV1 were found in close proximity to 5-HT+ paraneurones. In vitro 5-HT (1 µm) stimulation of urethral primary afferent neurones, mimicking 5-HT release from paraneurones, elicited changes in the intracellular calcium concentration ([Ca2+]i) mediated by 5-HT2 and 5-HT3 receptors. Approximately 50% of 5-HT responding cells also responded to capsaicin with changes in the [Ca2+]i. In vivo intra-urethral 5-HT application increased VMRs induced by urethral distention and activated pERK in lumbosacral spinal cord neurones. Conclusion These morphological and functional findings provide insights into a putative paraneurone-neural network within the urethra that utilizes 5-HT signalling, presumably from paraneurones, to modulate primary sensory pathways carrying nociceptive and non-nociceptive (mechano-sensitive) information to the central nervous system.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing

et al. 2017

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“…It must be mentioned that we deliberately limited the study to females due the existence of 5‐HT cells in the prostatic ducts suggesting an involvement of the monoamine in the regulation of prostatic activity . Furthermore, anatomic equivalence between human and rat male urethra is poor.…”

Section: Discussionmentioning

confidence: 99%

“…Populations of specialized cells have been identified in the urethral epithelium of several mammalian species, 8,[12][13][14][15] including humans. 16,17 Electron microscopy studies identified cells with apical microvilli and basal secretory granules expressing acetylcholine (ACh) and serotonin (5-HT).…”

Section: Introductionmentioning

confidence: 99%

Evidence for an urethro‐vesical crosstalk mediated by serotonin

Coelho

Oliveira

Cavaleiro

et al. 2018

Neurourology and Urodynamics

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Innervation of the Epithelium and Lamina Propria of the Urethra of the Female Rat

Eggermont

Wachter

Eastham

et al. 2018

The Anatomical Record

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The aim of this study was to characterize the number, type and distribution of immunochemically identified nerves in epithelium and lamina propria of the female rat urethra. Urethras from female Sprague-Dawley rats (n = 12) were fixed, frozen and sectioned (8 μm). Standard immunohistochemical techniques were used to identify putative nerves using the following antibodies: calcitonin gene related peptide (cgrp), neuronal nitric oxide synthase (nNos), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (vacht). The number, distribution and characteristics of all immunoreactive (IR) structures adjacent to the urethral epithelium and in the lamina propria was assessed. In the bladder, few cgrp-IR and vacht-IR fibers were associated with the urothelium or suburothelium of the lateral wall. In contrast, large numbers of vacht-IR, nNos-IR and cgrp-IR fibers were found close to the epithelium and subepithelium of the bladder neck and throughout the urethra. The number of cgrp-IR fibers was significantly higher in the urethra in comparison with the bladder neck. A population of undescribed cgrp-IR cells associated with the bladder neck and proximal urethra has been characterized. Each of these cells appears to be associated with a nerve fiber. In the distal urethra, the number of peptidergic fibers penetrating the epithelium was significantly higher than the rest of the urethra. Clearly, this study has revealed a highly complex and heterogeneous network of putative afferent nerves fibers along the length of the urethra. These structural specializations need to be taken into account when probing the different functions of the urethra. Anat Rec, 302:201-214, 2019. © 2019 players.brightcove.net/656326989001/default_default/index.html? videoId=5988401873001 BB = bladder base; BN = bladder neck; det = detrusor; DU = distal urethra; epi = epithelium; F = epithelial folds; lp = lamina propria; lum = lumen; LW = bladder lateral wall; MU = mid urethra; PU = proximal urethra; sm = smooth muscle; ss = striated muscle sphincter

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Topographic distribution of serotonin-immunoreactive urethral endocrine cells and their relationship with calcitonin gene-related peptide-immunoreactive nerves in male rats

Cited by 11 publications

References 26 publications

Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing

Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing

Evidence for an urethro‐vesical crosstalk mediated by serotonin

Innervation of the Epithelium and Lamina Propria of the Urethra of the Female Rat

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