Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle

Neurourol Urodyn. 2014 Jun;33(5):558-65. doi: 10.1002/nau.22434. Epub 2013 Jul 12.

Abstract

Aims: The current study investigates the role played by bradykinin (BK) receptors in the contractility to the pig bladder neck smooth muscle.

Methods: Bladder neck strips were mounted in myographs for isometric force recordings and BK receptors expression was also determined by immunohistochemistry.

Results: B2 receptor expression was observed in the muscular layer and urothelium whereas B1 expression was consistent detected in urothelium. A strong B2 immunoreactivity was also observed within nerve fibers among smooth muscle bundles. On urothelium-denuded preparations basal tone, BK induced concentration-dependent contractions which were reduced in urothelium-intact samples, by extracellular Ca(2+) removal and by blockade of B2 receptors and voltage-gated Ca(2+) (VOC) and non-VOC channels, and increased by cyclooxygenase (COX) inhibition. On phenylephrine-precontracted denuded strips, under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. In urothelium-intact samples, the B1 receptor agonist kallidin promoted concentration-dependent relaxations which were reduced by blockade of B1 receptors, COX, COX-1 and large-conductance Ca(2+) -activated K(+) (BKCa ) channels and abolished in urothelium-denuded samples and in K(+) -enriched physiological saline solution-precontracted strips.

Conclusions: These results suggest that BK produces contraction of pig bladder neck via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry via VOC and non-VOC channels with a minor role for intracellular Ca(2+) mobilization. Facilitatory neuronal B2 receptors modulating NANC inhibitory neurotransmission and urothelial B1 receptors producing relaxation via the COX-1 pathway and BKCa channel opening are also demonstrated. Neurourol. Urodynam. 33:558-565, 2014. © 2013 Wiley Periodicals, Inc.

Keywords: bladder neck; bradykinin receptors; neuronal; smooth muscle contractility; urothelial and smooth muscle receptors and inhibitory neurotransmission modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Bradykinin Receptor Antagonists / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Cyclooxygenase 1 / metabolism
  • Immunohistochemistry
  • In Vitro Techniques
  • Isometric Contraction / drug effects
  • Isometric Contraction / physiology
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth / physiology
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Receptor, Bradykinin B1 / metabolism*
  • Receptor, Bradykinin B1 / physiology
  • Receptor, Bradykinin B2 / metabolism*
  • Receptor, Bradykinin B2 / physiology
  • Signal Transduction
  • Swine
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism*
  • Urinary Bladder / physiology
  • Urothelium / drug effects
  • Urothelium / metabolism*

Substances

  • Bradykinin Receptor Antagonists
  • Calcium Channels
  • Large-Conductance Calcium-Activated Potassium Channels
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • Cyclooxygenase 1
  • Prostaglandin-Endoperoxide Synthases
  • Bradykinin
  • Calcium