STIMULATION OF CYCLIC-GMP PRODUCTION VIA A NITROSYL FACTOR IN SENSORYNEURONAL CULTURES BY ALGESIC OR INFLAMMATORY AGENTS

Capsaicin stimulates cyclic GMP production via nitric oxide (NO) (or a nother nitrosyl factor) in dorsal root ganglion (DRG) neurons maintain ed in culture. The purpose of the present study was to characterize fu rther capsaicin stimulation of cyclic GMP production in DRG cells main tained in culture, investigate other algesic and/or inflammatory agent s for effects on cyclic GMP production, and examine cells responsible for NO production and cyclic GMP production. Capsaicin stimulation of cyclic GMP production in DRG cells was dose dependent, receptor mediat ed, and attenuated by hemoglobin, Prostaglandin E(2), substance P, and calcitonin gene-related peptide did not affect basal, capsaicin-stimu lated, or bradykinin-stimulated cyclic GMP production. Other inflammat ory or algesic agents, including serotonin, histamine, ATP, glutamate, aspartate, and NMDA, did not af feet cyclic GMP production. Pretreatm ent of DRG cells with lipopolysaccharide increased basal cyclic GMP pr oduction in neuronal but not in nonneuronal cultures and facilitated s timulation of cyclic GMP production by L-arginine. Capsaicin pretreatm ent of neuronal DRG cultures, which destroys capsaicin-sensitive (smal l diameter) afferent neurons, attenuated capsaicin- and bradykinin-sti mulated cyclic GMP production but did not affect basal or sodium nitro prusside-stimulated cyclic GMP production. These results indicate that capsaicin elicits production of a nitrosyl factor via capsaicin-sensi tive (small diameter) neurons. Capsaicin evoked cyclic GMP production in nonneuronal DRG cultures in the presence but not in the absence of apposed neuronal DRG cultures. Overall, these findings suggest that sp ecific exogenous (or endogenous) substances may stimulate production o f a nitrosyl factor(s) by a subset of DRG neurons, and nitrosyl factor s produced by these neurons may affect cyclic GMP production in neighb oring neuronal or nonneuronal cells.