Changes in tracheo-bronchial sensory neuropeptide receptor gene expression pattern in rats with cisplatin-induced sensory neuropathy.
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.
Horváth
Péter
P
DEOEC, Department of Pharmacology, Nagyerdei krt. 98, Debrecen, Hungary.
Szilvássy
Zoltán
Z
Peitl
Barna
B
Szilvássy
Judit
J
Helyes
Zsuzsanna
Z
Szolcsányi
János
J
Németh
József
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D002945:Cisplatin / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000097:blood; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009443:Neuritis / Q000139:chemically induced / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics; D018040:Receptors, Neurokinin-1 / Q000235:genetics; D018041:Receptors, Neurokinin-2 / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics*; D013004:Somatostatin / Q000097:blood; D013373:Substance P / Q000097:blood / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D018015:Receptors, Calcitonin Gene-Related Peptide; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D017481:Receptors, Somatostatin; D013373:Substance P; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide; D002945:Cisplatin