Sodium nitroprusside evokes the release of immunoreactive calcitonin gene-related peptide and substance P from dorsal horn slices via nitric oxide-dependent and nitric oxide-independent mechanisms.
The results of behavioral studies suggest that nitric oxide (NO) participates in certain spinal mechanisms that contribute to hyperalgesia. Additionally, previous studies indicate that the release of immunoreactive calcitonin gene-related peptide (iCGRP) and substance P (iSP) is increased in the dorsal horn of the spinal cord during hyperalgesia. Therefore, the aim of this study was to determine whether NO acts to enhance peptide release in the dorsal horn of rats using an in vitro superfusion technique. Sodium nitroprusside (SNP) was used as an NO donor. The results of this study indicate that SNP caused a dose-related, calcium-dependent increase in the release of iCGRP and iSP from dorsal horn slices of the rat spinal cord. Furthermore, pretreatment with SNP reduced the ability of capsaicin to evoke the release of either peptide, suggesting that a target for SNP exists on certain capsaicin-sensitive primary afferent terminals. In addition to increasing peptide release, SNP also caused a significant five to sixfold increase in the levels of immunoreactive guanosine 3',5'-monophosphate (i-cGMP) in the dorsal horn. This SNP-evoked increase was significantly decreased by the guanylate cyclase inhibitor methylene blue in a dose-dependent manner. In addition, the release of iCGRP was also significantly reduced in the presence of methylene blue, although the relationship between peptide release and i-cGMP production remains unclear. Sodium nitroprusside-evoked peptide release was significantly reduced in the presence of hemoglobin (an oxide radical scavenger), suggesting that the drug effect was due to the generation of NO. However, the release of iCGRP and iSP was also evoked by sodium ferricyanide (the coproduct of SNP) and by 7-d-old, photoinactivated SNP.(ABSTRACT TRUNCATED AT 250 WORDS)
Garry
M G
MG
Department of Restorative Sciences, University of Minnesota Dental School, Minneapolis 55455.
Richardson
J D
JD
Hargreaves
K M
KM
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D005292:Ferricyanides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
D005292:Ferricyanides; C035579:sodium ferricyanide; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin