New evidence on the mechanisms underlying bradykinin-mediated contraction of the pig iris sphincter in vitro

Peptides. 2003 Jul;24(7):1045-51. doi: 10.1016/s0196-9781(03)00182-7.

Abstract

We have reported previously that bradykinin (BK) induces potent and reproducible concentration-dependent contractions of the pig iris sphincter (PIS) muscle in vitro through the activation of BK B(2) receptors. Here we attempted to investigate additional mechanisms by which BK induces contraction of the PIS in vitro. BK-mediated contraction of the PIS relied largely on the external Ca2+ influx by a mechanism sensitive to the L-, N- and P-type of Ca2+ channel selective blockers. Likewise, BK-induced contraction of the PIS was greatly inhibited by the CGRP-(8-37), NK(2) or NK(3) receptor antagonists (SR 48968, SR 142801), and to a lesser extent by the NK(1) antagonist (FK 888). Capsaicin desensitization of PIS or capsazepine pre-incubation also significantly reduced BK-mediated contraction in the PIS. Furthermore, KT 5720 or GF 109203X (the protein kinase A and C inhibitors, respectively) also significantly inhibited BK-mediated contraction. Taken together, these results indicate that BK-mediated contraction of the PIS seems to be mediated primarily by the release of CGRP and tachykinins from sensory nerve fibers, and relies largely on extracellular Ca2+ influx via activation of L-, N- and P-type of Ca2+ channels. Finally, these responses are mediated by activation of both protein kinase A- and C-dependent mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Bradykinin / pharmacology*
  • Bradykinin / physiology
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels / physiology
  • Capsaicin / analogs & derivatives*
  • Capsaicin / pharmacology
  • Carbazoles / pharmacology
  • Conotoxins / pharmacology
  • Dipeptides / pharmacology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Iris / drug effects
  • Iris / physiology*
  • Maleimides / pharmacology
  • Muscle Contraction / drug effects*
  • Nicardipine / pharmacology
  • Peptide Fragments / pharmacology
  • Piperidines / pharmacology
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism
  • Pyrroles / pharmacology
  • Receptors, Calcitonin Gene-Related Peptide / physiology
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / physiology
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Receptors, Neurokinin-2 / physiology
  • Receptors, Neurokinin-3 / antagonists & inhibitors
  • Receptors, Neurokinin-3 / physiology
  • Swine
  • Tachykinins / physiology
  • omega-Agatoxin IVA / pharmacology

Substances

  • Benzamides
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Calcium Channels
  • Carbazoles
  • Conotoxins
  • Dipeptides
  • Indoles
  • Maleimides
  • Peptide Fragments
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrroles
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Drug
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • Tachykinins
  • omega-Agatoxin IVA
  • calcitonin gene-related peptide (8-37)
  • FK 888
  • Egtazic Acid
  • KT 5720
  • SR 48968
  • Nicardipine
  • Protein Kinases
  • Calcitonin Gene-Related Peptide
  • SR 142801
  • bisindolylmaleimide I
  • capsazepine
  • Capsaicin
  • Bradykinin
  • Calcium