title: Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstruction.
abstract: OBJECTIVE
  Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor.
  
  
  METHODS
  Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits.
  
  
  RESULTS
  The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 microM.
  
  
  CONCLUSIONS
  The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue.
authors.affiliation: Department of Pathobiology, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. labelle@vet.upenn.edu
authors.forename: Edward
authors.initials: E
authors.lastname: LaBelle
authors.forename: Stephen
authors.initials: S
authors.lastname: Zderic
authors.forename: Daniel
authors.initials: D
authors.lastname: Delaney
authors.forename: Joseph
authors.initials: J
authors.lastname: Hypolite
authors.forename: Alan
authors.initials: A
authors.lastname: Wein
authors.forename: Samuel
authors.initials: S
authors.lastname: Chacko
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D066298:In Vitro Techniques; D008055:Lipids / Q000502:physiology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D008055:Lipids; D018721:Muscarinic Agonists; D010743:Phospholipids; D016718:Arachidonic Acid; D002217:Carbachol; D010741:Phospholipases A; D054467:Phospholipases A2