title: Localization of soluble guanylyl cyclase in the superficial dorsal horn.
abstract: Nitric oxide (NO) has been implicated in pain processing at the spinal level, but the mechanisms mediating its effects remain unclear. In the present work, we studied the organization of the major downstream effector of NO, soluble guanylyl cyclase (sGC), in the superficial dorsal horn of rat. Almost all neurokinin 1 (NK1) receptor-positive neurons in lamina I (a major source of ascending projections) were strongly immunopositive for sGC. Many local circuit neurons in laminae I-II also stained for sGC, but less intensely. Numerous fibers, presumably of unmyelinated primary afferent (C fiber) origin, stained for calcitonin gene-related peptide or isolectin B4, but none of these was immunopositive for sGC. These data, along with immunoelectron microscopy results, imply that unmyelinated primary afferent fibers terminating in the superficial dorsal horn lack sGC. Double labeling showed that neuronal nitric oxide synthase (nNOS) seldom colocalized with sGC, but nNOS-positive structures were frequently closely apposed to sGC-positive structures, suggesting that in the superficial dorsal horn NO acts mainly in a paracrine manner. Our data suggest that the NK1 receptor-positive projection neurons in lamina I are a major target of NO released in superficial dorsal horn. NO may also influence local circuit neurons, but it does not act on unmyelinated primary afferent terminals via sGC.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, 27599, USA.
authors.forename: Jin-Dong
authors.initials: JD
authors.lastname: Ding
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Weinberg
mesh_terms: D000344:Afferent Pathways / Q000201:enzymology / Q000648:ultrastructure; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D006162:Guanylate Cyclase; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D036421:Nerve Fibers, Unmyelinated / Q000201:enzymology; D009433:Neural Inhibition / Q000502:physiology; D009475:Neurons, Afferent / Q000201:enzymology / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009619:Nociceptors / Q000201:enzymology*; D010146:Pain / Q000201:enzymology* / Q000503:physiopathology; D019899:Paracrine Communication / Q000502:physiology; D037121:Plant Lectins; D020671:Posterior Horn Cells / Q000201:enzymology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000201:enzymology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D013126:Spinal Nerve Roots / Q000201:enzymology / Q000648:ultrastructure; D013133:Spinothalamic Tracts / Q000201:enzymology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D018160:Receptors, Cytoplasmic and Nuclear; D018040:Receptors, Neurokinin-1; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D015740:Calcitonin Gene-Related Peptide