Abstract
Purpose We investigated the neurohumoral modulation of the contractility of bladder muscularis mucosae (mucosa) compared with that of detrusor smooth muscle. Materials and Methods Changes in the contractility of mucosal and detrusor bundles from guinea pig bladders were measured using isometric tension recording. The morphological relationship between the muscularis mucosae and blood vessels, and their sensory innervation was examined by fluorescence immunohistochemistry. Results Meshworks of muscularis mucosae with numerous branches and anastomosis preferentially ran parallel with suburothelial blood vessels. Although PTHrPRs (parathyroid hormone-related peptide receptors) were expressed in detrusor and mucosa, the endogenous detrusor relaxant PTHrP (parathyroid hormone-related peptide) (1 nM) suppressed spontaneous contractions in detrusor but not in mucosa. A higher concentration of PTHrP (10 nM) was required to inhibit mucosal contractility. Capsaicin (1 μM) abolished spontaneous contractions in mucosa but had an excitatory action on detrusor contractility. hCGRP (human calcitonin gene-related peptide) (1 nM) attenuated spontaneous mucosal contractions. Pretreatment with the CGRP (calcitonin gene-related peptide) antagonist hCGRP 8-37 (2 μM) inhibited CGRP or capsaicin induced suppression of spontaneous contractions. Consistently, CGRP immunoreactive primary afferent nerves were abundant in muscularis mucosae. Conclusions Co-localization of muscularis mucosae with the suburothelial microvasculature suggests that spontaneous contractions of mucosa might function to prevent microvasculature stretching upon bladder wall distension during the storage phase. It is likely that PTHrP selectively suppresses spontaneous contractions in detrusor but not in mucosa. Thus, endogenous PTHrP may well increase bladder compliance without an associated distension induced deformation of mucosal elements. Excessive stimulations of sensory nerves may suppress mucosal contractility by releasing CGRP.
| Original language | English |
|---|---|
| Pages (from-to) | 1287-1294 |
| Number of pages | 8 |
| Journal | Journal of Urology |
| Volume | 196 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Oct 1 2016 |
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All Science Journal Classification (ASJC) codes
- Urology
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Role of PTHrP and Sensory Nerve Peptides in Regulating Contractility of Muscularis Mucosae and Detrusor Smooth Muscle in the Guinea Pig Bladder. / Lee, Ken; Mitsui, Retsu; Kajioka, Shunichi; Naito, Seiji; Hashitani, Hikaru.
In: Journal of Urology, Vol. 196, No. 4, 01.10.2016, p. 1287-1294.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Role of PTHrP and Sensory Nerve Peptides in Regulating Contractility of Muscularis Mucosae and Detrusor Smooth Muscle in the Guinea Pig Bladder
AU - Lee, Ken
AU - Mitsui, Retsu
AU - Kajioka, Shunichi
AU - Naito, Seiji
AU - Hashitani, Hikaru
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Purpose We investigated the neurohumoral modulation of the contractility of bladder muscularis mucosae (mucosa) compared with that of detrusor smooth muscle. Materials and Methods Changes in the contractility of mucosal and detrusor bundles from guinea pig bladders were measured using isometric tension recording. The morphological relationship between the muscularis mucosae and blood vessels, and their sensory innervation was examined by fluorescence immunohistochemistry. Results Meshworks of muscularis mucosae with numerous branches and anastomosis preferentially ran parallel with suburothelial blood vessels. Although PTHrPRs (parathyroid hormone-related peptide receptors) were expressed in detrusor and mucosa, the endogenous detrusor relaxant PTHrP (parathyroid hormone-related peptide) (1 nM) suppressed spontaneous contractions in detrusor but not in mucosa. A higher concentration of PTHrP (10 nM) was required to inhibit mucosal contractility. Capsaicin (1 μM) abolished spontaneous contractions in mucosa but had an excitatory action on detrusor contractility. hCGRP (human calcitonin gene-related peptide) (1 nM) attenuated spontaneous mucosal contractions. Pretreatment with the CGRP (calcitonin gene-related peptide) antagonist hCGRP 8-37 (2 μM) inhibited CGRP or capsaicin induced suppression of spontaneous contractions. Consistently, CGRP immunoreactive primary afferent nerves were abundant in muscularis mucosae. Conclusions Co-localization of muscularis mucosae with the suburothelial microvasculature suggests that spontaneous contractions of mucosa might function to prevent microvasculature stretching upon bladder wall distension during the storage phase. It is likely that PTHrP selectively suppresses spontaneous contractions in detrusor but not in mucosa. Thus, endogenous PTHrP may well increase bladder compliance without an associated distension induced deformation of mucosal elements. Excessive stimulations of sensory nerves may suppress mucosal contractility by releasing CGRP.
AB - Purpose We investigated the neurohumoral modulation of the contractility of bladder muscularis mucosae (mucosa) compared with that of detrusor smooth muscle. Materials and Methods Changes in the contractility of mucosal and detrusor bundles from guinea pig bladders were measured using isometric tension recording. The morphological relationship between the muscularis mucosae and blood vessels, and their sensory innervation was examined by fluorescence immunohistochemistry. Results Meshworks of muscularis mucosae with numerous branches and anastomosis preferentially ran parallel with suburothelial blood vessels. Although PTHrPRs (parathyroid hormone-related peptide receptors) were expressed in detrusor and mucosa, the endogenous detrusor relaxant PTHrP (parathyroid hormone-related peptide) (1 nM) suppressed spontaneous contractions in detrusor but not in mucosa. A higher concentration of PTHrP (10 nM) was required to inhibit mucosal contractility. Capsaicin (1 μM) abolished spontaneous contractions in mucosa but had an excitatory action on detrusor contractility. hCGRP (human calcitonin gene-related peptide) (1 nM) attenuated spontaneous mucosal contractions. Pretreatment with the CGRP (calcitonin gene-related peptide) antagonist hCGRP 8-37 (2 μM) inhibited CGRP or capsaicin induced suppression of spontaneous contractions. Consistently, CGRP immunoreactive primary afferent nerves were abundant in muscularis mucosae. Conclusions Co-localization of muscularis mucosae with the suburothelial microvasculature suggests that spontaneous contractions of mucosa might function to prevent microvasculature stretching upon bladder wall distension during the storage phase. It is likely that PTHrP selectively suppresses spontaneous contractions in detrusor but not in mucosa. Thus, endogenous PTHrP may well increase bladder compliance without an associated distension induced deformation of mucosal elements. Excessive stimulations of sensory nerves may suppress mucosal contractility by releasing CGRP.
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U2 - 10.1016/j.juro.2016.04.082
DO - 10.1016/j.juro.2016.04.082
M3 - Article
VL - 196
SP - 1287
EP - 1294
JO - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 4
ER -