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Journal of Neuroscience, Vol 4, 3101-3111, Copyright © 1984 by Society for Neuroscience
Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species
SJ Gibson, JM Polak, SR Bloom, IM Sabate, PM Mulderry, MA Ghatei, GP McGregor, JF Morrison, JS Kelly and RM Evans
Calcitonin gene-related peptide (CGRP) immunoreactivity was found
throughout the entire spinal cord of man, marmoset, horse, pig, cat, guinea
pig, mouse, rat, and frog. CGRP-immunoreactive fibers were most
concentrated in the dorsal horn. In the ventral horn of some species large
immunoreactive cells, tentatively characterized as motoneurons, were
present. Pretreatment of rats with colchicine enhanced staining of these
large cells but did not reveal CGRP-immunoreactive cell bodies in the
dorsal horn. In the dorsal root ganglia, CGRP immunoreactivity was observed
in most of the small and some of the intermediate sized cells. Substance P
immunoreactivity, where present, was co-localized with CGRP to a proportion
of the small cells. In the cat the ratio of substance P- immunoreactive to
CGRP-immunoreactive ganglion cells was 1:2.7 (p less than 0.001). The
concentration of CGRP-immunoreactive material in tissue extracts was
determined by radioimmunoassay. In the dorsal horn of the rat spinal cord
the levels of peptide were found to range from 225.7 +/- 30.0 pmol/gm of
wet weight in the cervical region to 340.6 +/- 74.6 pmol/gm in the sacral
spinal cord. In the rat ventral spinal cord, levels of 15.7 +/- 2.7 to 35.1
+/- 10.6 pmol/gm were found. The concentration in dorsal root ganglia of
the lumbar region was 225.4 +/- 46.9 pmol/gm. Gel permeation chromatography
of this extractable CGRP- like immunoreactivity revealed three distinct
immunoreactive peaks, one eluting at the position of synthetic CGRP and the
others, of smaller size, eluting later. In cats and rats, rhizotomy induced
a marked loss of CGRP-immunoreactive fibers from the dorsal horn of the
spinal cord. In the cat, unilateral lumbosacral dorsal rhizotomy resulted
in a significant (p less than 0.05) reduction of extractable CGRP from the
ipsilateral lumbar dorsal horn (5.6 +/- 1.2 pmol/gm of wet weight) compared
to the contralateral side (105.0 +/- 36.0 pmol/gm of wet weight). We
conclude that the major origin of CGRP in the dorsal spinal cord is
extrinsic, from afferent fibers which are probably derived from cells in
the dorsal root ganglia. The selective distribution of CGRP throughout
sensory, motor, and autonomic areas of the spinal cord suggests many
putative roles for this novel peptide.
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