Changes in tracheo-bronchial sensory neuropeptide receptor gene expression pattern in rats with cisplatin-induced sensory neuropathy

Neuropeptides. 2006 Feb;40(1):77-83. doi: 10.1016/j.npep.2005.10.007. Epub 2005 Dec 15.

Abstract

An attenuated neurogenic broncho-constriction underpinned by a decrease in sensory neuropeptide release has been shown to be characteristic of cisplatin-induced neuropathy. The present work was to explore if beyond neuropeptide release, cisplatin at a treatment schedule attaining sensory neuropathy, produced changes in the expression of the receptors of sensory neuropeptides such as somatostatin, calcitonin gene-related peptide (CGRP) and substance P (SP) in bronchial tissue of the rat. Twenty-four Wistar rats were divided into three groups. The animals in the "Treatment groups 1 and 2" were given cisplatin (1.5mgkg(-1)) and mannitol (75mgkg(-1)) over 5 days. The rats in the "Control" group were given mannitol+isotonic saline. Four animals from each group were used to study the expression pattern of the neuropeptide receptors in bronchial tissue. The levels of somatostatin receptor 4 (SSTR 4), neurokinin 1 (NK1), neurokinin 2 (NK2) and CGRP receptor expression were examined by quantitative real time polymerase chain reaction (RT-PCR) method, 11 and 22 days after the last cisplatin/vehicle dose. The cisplatin treatment significantly increased plasma somatostatin immunoreactivity and the expression of SSTR4 receptor detected both on the 11th and 22nd post-treatment days with no change in either CGRP, NK1, and NK2 receptor gene expression or plasma CGRP and substance P levels. We conclude that cisplatin neuropathy is accompanied by an increase in plasma somatostatin immunoreactivity with an increase in SSTR4 expression in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Calcitonin Gene-Related Peptide / blood
  • Cisplatin / adverse effects*
  • Gene Expression Regulation / drug effects
  • Insulin / blood
  • Neural Conduction / drug effects
  • Neural Conduction / physiology
  • Neuritis / chemically induced
  • Neuritis / physiopathology*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Wistar
  • Receptors, Calcitonin Gene-Related Peptide / genetics
  • Receptors, Neurokinin-1 / genetics
  • Receptors, Neurokinin-2 / genetics
  • Receptors, Somatostatin / genetics*
  • Somatostatin / blood
  • Substance P / blood
  • Substance P / genetics

Substances

  • Blood Glucose
  • Insulin
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Somatostatin
  • Substance P
  • Somatostatin
  • Calcitonin Gene-Related Peptide
  • Cisplatin