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-asparta te at the level of the spinal cord. One possible mechanism for this ac tion is that nitric oxide increases transmitter release from the prima ry afferent nociceptors that synapse in the dorsal horn of the spinal cord. To address this possibility, we investigated whether various nit ric oxide donors and cyclic guanosine 3',5'-monophosphate could alter the release of substance P and calcitonin gene-related peptide from ra t sensory neurons in culture. Sodium nitroprusside (100 nM to 100 mu M ) had little effect on basal release of either peptide, but it signifi cantly increased the release of substance P and calcitonin gene-relate d peptide induced by 50 nM capsaicin. In contrast, sodium nitroprussid e 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-evok ed peptide release, although they induced a marked elevation in the in tracellular cyclic guanosine 3',5'-monophosphate levels. Pretreating t he 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 capsaic in-induced release from sensory neurons. Moreover, pretreating the cel ls with the nitric oxide synthase inhibitor, N-G-nitro-L-arginine (100 mu M), abolished the rise in cyclic guanosine 3',5'-monophosphate ind uced by capsaicin without altering capsaicin-stimulated release of eit her peptide. These data suggest that neither nitric oxide nor cyclic g uanosine 3',5'-monophosphate are involved in enhancing peptide release from sensory neurons and that capsaicin-induced release is not mediat ed by cyclic guanosine 3',5'-monophosphate.