title: Role of PTHrP and Sensory Nerve Peptides in Regulating Contractility of Muscularis Mucosae and Detrusor Smooth Muscle in the Guinea Pig Bladder.
abstract: OBJECTIVE
  We investigated the neurohumoral modulation of the contractility of bladder muscularis mucosae (mucosa) compared with that of detrusor smooth muscle.
  
  
  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.
authors.affiliation: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: leeken91@med.nagoya-cu.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Retsu
authors.initials: R
authors.lastname: Mitsui
authors.affiliation: Department of Applied Urology and Molecular Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kajioka
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.affiliation: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D009092:Mucous Membrane / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D001743:Urinary Bladder / Q000166:cytology / Q000294:innervation* / Q000502:physiology
chemical_list: D044162:Parathyroid Hormone-Related Protein
keywords: blood vessels; mucous membrane; muscle, smooth; parathyroid hormone-related protein; urinary bladder