Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat

Wiesenfeld‐Hallin, Zsuzsanna; Hökfelt, Tomas; Lundberg, Jan M.; Forssmann, W. G.; Reinecke, Manfred; Tschopp, Fritz A.; Fischer, Jan A.

doi:10.1016/0304-3940(84)90374-4

Cited by 561 publications

(129 citation statements)

References 15 publications

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“…The expression patterns of L1, CGRP, IB4, and P2X 3 immunoreactivity in the superficial dorsal horn of adult wild-type mice resemble those reported in adult rats ( Fig. 1; Wiesenfeld-Hallin et al, 1984;Silverman and Kruger, 1990;Vulchanova et al, 1998;Runyan et al, 2005;Jakeman et al, 2006). L1 is concentrated in Lissauer's Tract, laminae I-II, and the dorsolateral funiculus (Figs.…”

supporting

confidence: 69%

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Runyan

Roy²,

Zhong³

et al. 2007

Neuroscience

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L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (6 segments; T10-L2) on both wildtype and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy. Keywordscell adhesion molecule; denervated; IB4; CGRP; nociceptors; rhizotomy The cell adhesion molecule L1 (L1 CAM) is an axonal glycoprotein and a member of the immunoglobulin superfamily (Kamiguchi et al., 1997). L1 plays a role in axonal outgrowth, fasciculation, and guidance during spinal cord development (Stallcup et al., 1985;Jessell, 1988;Stoeckli and Landmesser, 1995;Orlino et al., 2000;Tran and Phelps, 2000;Akopians et al., 2003) through homophilic and various heterophilic binding partners such as integrins (αVβ3 and α5β1) and the fibroblast growth factor receptor (Kamiguchi and Lemmon, 1997 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Lemmon, 1997;Castellani et al., 2000). NIH Public AccessMutations in X-linked L1 in humans cause major developmental errors and result in a group of symptoms that include corpus callosum hypoplasia, spastic paraplegia and hydrocephalus (Fran...

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supporting

confidence: 69%

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Runyan

Roy²,

Zhong³

et al. 2007

Neuroscience

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“…In the sensory ganglia, it is known that various peptides occur within the same neurons, and fibers with certain combinations of peptides project to a distinctive peripheral target area (Gibbins et al 1987 ;Molander et al 1987). There are neurons containing both SP and CGRP (SP/CGRP) and neurons containing CGRP alone (CGRP/-) in the DRG (Wiesenfeld-Hallin et al 1984 ;Ju et al 1987). In the present study, about 35% of the DRG cells retrogradely labeled with FB were immunoreactive to both SP and CORP.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Study of the Sympathetic and Sensory Innervation to the Blood Vessels of the Dog Forepaw.

Tsuruta

Masuko

Watanabe

1992

Tohoku J. Exp. Med.

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Immunohistochemical staining of arteries supplying the dog forepaw showed a dense distribution of nerve fibers which were immunoreactive to tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) around the vascular walls. The density of each immunoreactive fiber tended to increase in the peripheral branch of the vascular tree. Retrograde axonal tracing with Fast Blue from the artery revealed that these immunoreactive fibers originated from NPY-containing catecholaminergic as well as VIP/SP/ CGRP-containing non-catecholaminergic neurons in the stellate ganglion and SP/ CGRP-containing neurons in the dorsal root ganglia of segments C, to Thl. After stellate ganglionectomy, TH-, NPY-, and, VIP-immunoreactive fibers disappeared completely from the arterial walls while approximately 40% of SP-and CGRPimmunoreactive fibers remained. The present results indicate that the artery of the dog forepaw receive triple innervation of adrenergic sympathetic, nonadrenergic sympathetic, and sensory fibers, and suggest that about 40% of SP-and CGRP-immunoreactive fibers are of sensory origin.

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“…CGRP-immunoreactivity is found in heart particularly around the sinoatrial and atrioventricular node, as well as in periadventitial nerves in association with blood vessels (Manson et al, 1984;Wisenfeld-Hallin et al, 1984;Mulderry et al, 1985;Gennari & Fischer, 1985).…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and mechanical effects of calcitonin gene‐related peptide on guinea‐pig atria

Ohmura

Nishio

Kigoshi

et al. 1990

British J Pharmacology

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1 The effects of calcitonin gene-related peptide (CGRP) on mechanical and electrophysiological responses were studied in the guinea-pig atrial muscle preparations and in single cells. 2 CGRP (>10-9M) enhanced the twitch contraction in a concentration-dependent manner in electrically driven left atria and increased heart rate in spontaneously beating right atria. The positive inotropic and chronotropic effects of CGRP were not inhibited by propranolol but were attenuated by reduction of the calcium concentration in the bathing medium. 3 In single left atrial cells, CGRP slightly hyperpolarized the resting potential but did not affect the other action potential parameters significantly. 4 Under whole-cell voltage-clamp conditions, CGRP increased the calcium inward current. The peptide also increased the steady inward current elicited by hyperpolarization and the late outward current by depolarization. 5 These results suggest that CGRP may produce the positive inotropic and presumably chronotropic effects by increasing calcium inward current. CGRP also increases the potassium permeability. Such effects on ionic currents may not produce any apparent change in the action potential conformation, due to their opposite directional actions and relatively weak potencies.

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Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat

Cited by 561 publications

References 15 publications

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Immunohistochemical Study of the Sympathetic and Sensory Innervation to the Blood Vessels of the Dog Forepaw.

Electrophysiological and mechanical effects of calcitonin gene‐related peptide on guinea‐pig atria

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