CGMP-DEPENDENT PROTEIN-KINASE IN DORSAL-ROOT GANGLION - RELATIONSHIP WITH NITRIC-OXIDE SYNTHASE AND NOCICEPTIVE NEURONS

Nitric oxide and cGMP influence plasticity of nociceptive processing i n spinal cord. However, effecters for cGMP have not been identified in sensory pathways. We now demonstrate that cGMP-dependent protein kina se I (cGKI) occurs in the DRGs at levels comparable to that in cerebel lum, the richest source of cGKI in the body. Immunohistochemical studi es reveal that cGKI is concentrated in a subpopulation of small- and m edium-diameter DRG neurons that partially overlap with substance P and calcitonin gene-related polypeptide containing cells. During developm ent, cGKI expression throughout the embryo is essentially restricted t o sensory neurons and to the spinal floor and roof plates. Neuronal ni tric oxide synthase (nNOS) is coexpressed with cGKI in sensory neurons during embryonic development and after peripheral nerve axotomy. The primary target for cGKI in cerebellum, G-substrate, is not present in developing, mature, or regenerating sensory neurons, indicating that o ther proteins serve as effecters for cGKI in sensory processing. These data establish sensory neurons as a primary locus for cGMP actions du ring development and suggest a role for cGKI in plasticity of nocicept ion.