Expression of spinal cord Fos protein in response to intrathecal adrenomedullin and CGRP in conscious rats.
Adrenomedullin (AM) immunoreactivity and mRNA, in addition to a large number of specific AM-binding sites, exist in the rat spinal cord. However, no phenotype has been reported for AM in the spinal cord. Here, expression of c-fos in response to intrathecal (i.t.) administration of AM, proadrenomedullin N-terminal 20 peptide (PAMP) and calcitonin gene-related peptide (CGRP) was examined in the thoracic, lumbar and sacral regions of spinal cord in conscious rats. Two hours after i.t. administration of either CGRP (2.5 and 10 microg) or AM (10 microg), the number of c-Fos immunoreactive nuclei was increased in all the spinal regions examined in this study, with the highest increase observed in the superficial dorsal horn. Few cells with c-fos immunoreactivity were found in the spinal cord of rats 2 h after i.t. injection of either saline or PAMP. Effects of AM (10 microg) and CGRP (2.5 microg) on c-fos expression were blocked when rats were pretreated with 40 microg of intrathecal CGRP8-37 (CGRP1 receptor antagonist). Fos-like immunoreactivity induced by i.t. CGRP and/or AM were also significantly abolished by i.t. administration of the nitric oxide (NO) inhibitor, l-NAME, indicating that endogenous NO is a necessary intermediary in CGRP and AM induced c-fos expression in the rat spinal cord. In conclusion, AM induces c-fos expression in rat spinal cord when administered intrathecally, with the pattern being similar to those produced by i.t. CGRP. Effects of the two peptides are sensitive to CGRP8-37 and l-NAME.
Department of Biochemistry, The Shiraz University of Medical Sciences, P.O. Box 1971 Shiraz, Iran.
M A
MA
Takhshid
A A
AA
Owji
M
M
Vasei
M R
MR
Panjehshahin
S M B
SM
Tabei
H R
HR
Tabatabaee
J
J
Ay
D053607:Adrenomedullin; D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; D053607:Adrenomedullin; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester