Nitric oxide and cyclic guanosine 3',5'-monophosphate do not alter neuropeptide release from rat sensory neurons grown in culture.
Recent studies demonstrate that nitric oxide and cyclic guanosine 3',5'-monophosphate may mediate hyperalgesia induced by N-methyl-D-aspartate at the level of the spinal cord. One possible mechanism for this action is that nitric oxide increases transmitter release from the primary afferent nociceptors that synapse in the dorsal horn of the spinal cord. To address this possibility, we investigated whether various nitric oxide donors and cyclic guanosine 3',5'-monophosphate could alter the release of substance P and calcitonin gene-related peptide from rat sensory neurons in culture. Sodium nitroprusside (100 nM to 100 microM) had little effect on basal release of either peptide, but it significantly increased the release of substance P and calcitonin gene-related peptide induced by 50 nM capsaicin. In contrast, sodium nitroprusside did not alter release evoked by 100 nM bradykinin or 30 mM KCl. Two other nitric oxide-donating compounds, S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine did not enhance resting or capsaicin-evoked peptide release, although they induced a marked elevation in the intracellular cyclic guanosine 3',5'-monophosphate levels. Pretreating the cultures with 8-bromo-cyclic guanosine 3',5'-monophosphate, (0.5 or 0.1 mM for 30 or 60 min) did not result in the enhancement of capsaicin-induced release from sensory neurons. Moreover, pretreating the cells with the nitric oxide synthase inhibitor, NG-nitro-L-arginine (100 microM), abolished the rise in cyclic guanosine 3',5'-monophosphate induced by capsaicin without altering capsaicin-stimulated release of either peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Dymshitz
J
J
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202-5120.
Vasko
M R
MR
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism
D009479:Neuropeptides; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin