Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand.
Secreted mammalian Ly6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is a recently identified, endogenous ligand of the alpha7 subunit of nicotinic acetylcholine receptors. SLURP-1 is also the causative gene for an autosomal recessive palmoplantar keratoderma, Mal de Meleda. Although the function of SLURP-1 in keratinocyte development and differentiation has been extensively studied, little is known about its role in the nervous system. In the present study, we analyzed SLURP-1 expression in the spinal cord of rats, as a number of studies suggest spinal nicotinic acetylcholine receptors are important modulators of pain transmission. We detected intense SLURP-1 immunoreactivity in the dorsal horn of the spinal cord, especially in lamina I and outer II. In dorsal root ganglia, SLURP-1 immunoreactivity was detected in small- to medium-sized neurons, where in situ hybridization also revealed the presence of SLURP-1 mRNA. Fluorescent labeling of SLURP-1 partially overlapped that of calcitonin-gene related peptide (CGRP) or substance P (SP) in both the spinal cord dorsal horn and glabrous skin, and electron microscopic analysis revealed colocalization of SLURP-1 with SP or CGRP, in large synaptic vesicles in terminals within the superficial layer of the spinal cord. Finally, sciatic nerve axotomy reduced levels of SLURP-1 immunoreactivity in parallel with that of SP and CGRP in the ipsilateral superficial dorsal horn. These findings suggest that SLURP-1 is expressed in a subset of primary peptidergic sensory neurons.
Moriwaki
Yasuhiro
Y
Department of Pharmacology, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Watanabe
Yosuke
Y
Shinagawa
Tomoe
T
Kai
Miho
M
Miyazawa
Mai
M
Okuda
Takashi
T
Kawashima
Koichiro
K
Yabashi
Atsuko
A
Waguri
Satoshi
S
Misawa
Hidemi
H
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009619:Nociceptors / Q000378:metabolism / Q000648:ultrastructure; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D013373:Substance P / Q000032:analysis / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000950:Antigens, Ly; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C545249:SLURP-1 protein, mouse; C545248:SLURP-1 protein, rat; C048963:SLURP1 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor; D013373:Substance P; D014568:Urokinase-Type Plasminogen Activator; D015740:Calcitonin Gene-Related Peptide