Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a central nervous system (CNS) injury, there is only an "abortive regeneration" of axons, while injured axons regenerate vividly in the peripheral nervous system (PNS). This difference is due, at least in part, to the existence in the periphery of Schwann cells and of growth promoting proteins they synthetize. One strategy to promote regrowth of central axons can be therefore, to modify (i.e. "peripheralize") the microenvironment by transplanting biologically active Schwann cells into the lesion site. In a rat model of traumatic paraplegia by inflation of a subdural microballoon, we performed syngeneic transplants of Schwann cells. These cells are cultured from adult dorsal root ganglia and can be kept in vitro for several months. They are transplanted in the injured spinal cord. The grafted Schwann cells are well integrated in the host tissue without detectable inflammatory reaction. Cystic cavitation and astrogliosis are reduced in grafted animals as compared to injured, non-grafted animals. The transplant is invaded by abundant, mainly unmyelinated axons which are immunoreactive for substance P, VIP or CGRP, i.e. transmitters known to be present in DRG afferents. Supraspinal afferents containing 5HT, TH or CCK accumulate at the rostral margin of the graft. Experimental procedures trying to stimulate the invasion of the graft by descending fibers, i.e. by inducing a chemoattraction are therefore of crucial importance for functional recovery.
 ...
PMID:[The transplantation of syngeneic Schwann cells in medullary lesions: results, limitations and perspectives]. 779 51

Two of the key early events in the development of the peripheral nervous system are the proliferation of neural crest precursor cells and their subsequent differentiation into different neural cell types. We present evidence that members of the fibroblast growth factor family, (FGF1 or FGF2) act directly on the neural crest cells in vitro to stimulate proliferation in the presence of serum. These findings correlate with in situ hybridisation analysis, which shows FGF2 mRNA is expressed in cells both in the neural tube and within newly formed sensory ganglia (dorsal root ganglia, DRG) at embryonic day 10 in the mouse, when neural crest precursors are proliferating within the DRG. This data infers an autocrine/paracrine loop for FGF regulation of proliferation. Evidence supporting this notion is provided by the finding that part of the endogenous proliferative activity in the NC cultures is related to FGF. It was also found, in early neural crest cultures, that exogenous FGF completely inhibited neuronal differentiation, probably as a direct consequence of its mitogenic activity. In order to stimulate neuronal differentiation significantly, it was necessary to remove the FGF and replace it with leukemia inhibitory factor (LIF) or related factors. Under these conditions, 50% of the cells differentiated into neurons, which developed a sensory neuron morphology and were immunoreactive for the sensory markers CGRP and substance P. These data support a model of neural crest development, whereby multipotential neural crest precursor cells are stimulated to divide by FGF and subsequent development into sensory neurons is regulated by LIF or other cytokines with a similar signalling mechanism.
 ...
PMID:FGF2 regulates proliferation of neural crest cells, with subsequent neuronal differentiation regulated by LIF or related factors. 782 Dec 19

Using in situ hybridization, the expression of the mRNA for a neuropeptide Y (NPY) receptor, was studied in lumbar (L) 4 and 5 dorsal root ganglia (DRGs) of normal rats and at various intervals after unilateral sciatic nerve transection. Twenty percent of all normal DRG neurons were NPY receptor mRNA-positive, and the majority of these neurons were of the small type, with only a few labelled medium-sized and large neurons. In L5 normal ganglia NPY receptor mRNA colocalized with substance P, calcitonin gene-related peptide and galanin mRNAs in small neurons, but not in medium-sized or large neurons containing these peptides. NPY receptor mRNA was not observed in somatostatin or nitric oxide synthase mRNA-positive neurons. Sciatic nerve transection induced a marked decrease in NPY receptor mRNA levels. However, in parallel there was a transient increase in the number of NPY receptor mRNA-positive small neuron profiles, but the intensity of labelling was mostly very low, although a few strongly labelled, small neuron profiles were also encountered. In addition, axotomy caused a marked increase in the number of NPY receptor mRNA-positive large neuron profiles in the ipsilateral DRGs, and they constituted 15-20% of counted DRG neuron profiles and 45-65% of counted large neuron profiles, 7-28 days after axotomy. In L5 DRGs, ipsilateral to the axotomy, NPY receptor mRNA colocalized with NPY mRNA in many large and some medium-sized neuron profiles, with galanin mRNA in some small, medium-sized and large neuron profiles and with vasoactive intestinal polypeptide mRNA in some small and medium-sized neuron profiles and a few large profiles. Occasionally, NPY receptor mRNA was observed in nitric oxide synthase mRNA-positive small neurons. In the dorsal horn, NPY receptor mRNA-positive small neurons were concentrated in lamina II at L4 and L5 levels, and were scattered in deeper laminae. No marked changes were observed ipsilateral to the axotomy. No NPY receptor mRNA-positive cells were found in the normal rat gracile nucleus, or in this nucleus after axotomy. These results show that a NPY receptor may be a prejunctional receptor in primary afferent neurons and play a role in the modulation of somatosensory information, both in normal and lesioned primary afferent DRG cells. However, axotomy induced a distinct shift in NPY receptor mRNA expression from small to large neurons, indicating that sensitivity to NPY is switched from one modality to another.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effect of peripheral axotomy on expression of neuropeptide Y receptor mRNA in rat lumbar dorsal root ganglia. 813 Sep 32

Nitric oxide and cGMP influence plasticity of nociceptive processing in spinal cord. However, effectors for cGMP have not been identified in sensory pathways. We now demonstrate that cGMP-dependent protein kinase I (cGKl) occurs in the DRGs at levels comparable to that in cerebellum, the richest source of cGKl in the body. Immunohistochemical studies reveal that cGKl is concentrated in a subpopulation of small- and medium-diameter DRG neurons that partially overlap with substance P and calcitonin gene-related polypeptide containing cells. During development, cGKl expression throughout the embryo is essentially restricted to sensory neurons and to the spinal floor and roof plates. Neuronal nitric oxide synthase (nNOS) is coexpressed with cGKl in sensory neurons during embryonic development and after peripheral nerve axotomy. The primary target for cGKl in cerebellum, G-substrate, is not present in developing, mature, or regenerating sensory neurons, indicating that other proteins serve as effectors for cGKl in sensory processing. These data establish sensory neurons as a primary locus for cGMP actions during development and suggest a role for cGKl in plasticity of nociception.
 ...
PMID:cGMP-dependent protein kinase in dorsal root ganglion: relationship with nitric oxide synthase and nociceptive neurons. 862 52

The present study investigated neuropeptide phenotypes of aged, as well as adult, mouse sensory neurons. Proportions of somatostatin (SOM), calcitonin gene related protein (CGRP) and neuropeptide Y (NPY) immunoreactive (ir)-neurons were lower in primary cultures from aged (2 years) mice than in those from adult (6 months) animals, but similar for substance P (SP) in the absence of exogenous nerve growth factor (NGF). Addition of NGF, significantly enhanced (P < 0.05) proportions of SP, NPY and CGRP ir-neurons in both adult and aged cultures, whereas SOM ir-neurons were not affected in either. Thus SP, CGRP, NPY and SOM phenotypes are retained in cultured aged DRG neurons and some phenotypes can remain sensitive to NGF regulation.
 ...
PMID:Regulation by nerve growth factor of neuropeptide phenotypes in primary cultured sensory neurons prepared from aged as well as adult mice. 871 44

Intracellular recordings were performed on isolated rat DRG neurons to investigate the changes in the membrane potential in response to substance P and the involved ionic mechanisms. The resting membrane potential examined was -58.9 +/- 8.2 mV (X +/- SE) (n = 81). The conduction velocities estimated were: 20.4 +/- 4.8 m/s (X +/- SE) ranging from 14.1 to 28.7 m/s (47/60) in type A(alpha beta) cell, 9.8 +/- 5.2 m/s (X +/- SE) ranging from 1.2 to 13.7 m/s (13/60 in type A(delta) and type C cell. In majority of the neurons bath application of SP (10(-7) - 3 x 10(-4) mol/L) induced marked membrane potential depolarization (56/60). The membrane conductance increased 24.6% in average from control value of 2.72 x 10(-8) S during SP-induced depolarization (n = 3). The reversal potential was between +40 - %50 mV (n = 3). When NaCl in BSS was substituted with choline chloride or containing TTX (10(-5) mol/L), the amplitude of SP-induced depolarization attenuated markedly but not incompletion eventually. When high (20 mmol/L) and low (0 mmol/L) Ca2+ BSS was used, the amplitude of SP-induced depolarization increased and decreased respectively. However, when BSS containing 10(-4) mol/L Cd2+ or 10(-2) mol/L TEA was used SP-induced depolarization was reduced. The above results indicate that SP-induced depolarization involves a rather multiple changes in ionic conductance.
 ...
PMID:[Effect of substance P on the somatic membrane of rat DRG neurons]. 875 84

Neuropeptides and neurotrophin receptors are regulated in primary sensory neurons in response to axonal injury, and axonal lesions are characteristic stigmata of aging primary sensory neurons. We have therefore examined the expression of neuropeptides and neurotrophin receptor mRNAs in 30-month-old (median survival age) Sprague-Dawley rats to see if similar adaptive mechanisms operate in senescence. The content of neuropeptides was examined with immunohistochemistry (IHC) and in situ hybridization (ISH), and the cellular mRNA expression of neurotrophin receptors was studied with ISH. All of the aged rats had symptoms of hind limb incapacity (posterior paralysis), but fore limbs did not seem affected. The size-distribution of neuronal profiles in cervical and lumbar dorsal root ganglia (DRGs) was similar in aged and young adult (2-3 months old) rats. In aged rats, the DRG neurons showed an increase in both immunolabelling and mRNA content of neuropeptide tyrosine (NPY), as well as an increased cellular expression of galanin mRNA. In the same animals, there were decreased cellular levels of calcitonin gene-related peptide (CGRP; IHC and ISH) and substance P (SP; IHC and ISH), while the difference in neuronal somatostatin (IHC and ISH) was small. The distribution of neuropeptide immunoreactivities in the dorsal horn of the corresponding spinal cord segments revealed a decreased labelling for CGRP-, SP-, and somatostatin-like immunoreactivities (LI) in the aged rats at both cervical and lumbar levels. NPY- and galanin-LI had a similar distribution in aged and young adult rats. NPY-immunoreactive fibers were also encountered in the dorsal column of aged but not young adult rats. ISH revealed that most of the primary sensory neurons express mRNA for the p75 low-affinity neurotrophin receptor (p75-LANR) and that there was no discernible difference between young adult and aged rats. The labelling intensity for mRNA encoding high-affinity tyrosine kinase receptors (TrkA, TrkB, and TrkC) was decreased in aged rat DRG neurons, while the percentage of neuronal profiles expressing mRNA for TrkA/B/C was similar in young adult and aged rats. The changed pattern of neuropeptide expression in primary sensory neurons of aged rats resembled that seen in young adult rats subjected to axonal injury of peripheral sensory nerves and may, thus, indicate aging-related lesions of sensory fibers. Since NPY is primarily present in large and galanin in small DRG neurons, the stronger effect on NPY as compared to galanin expression may indicate that aging preferentially affects neurons associated with mechanoreception (A alpha and A beta fibers) as compared to nociceptive units (A delta and C fibers). Furthermore, the observed changes in neuropeptide expression were most pronounced in lumbar DRGs, that harbors the sensory neurons supplying the affected hindlimbs of the rats.
 ...
PMID:Neuropeptides and neurotrophin receptor mRNAs in primary sensory neurons of aged rats. 891 32

Using immunohistochemistry and in situ hybridization the in vivo effects of acidic and basic fibroblast growth factor (aFGF, bFGF), and of nerve growth factor (NGF) on the expression of galanin, neuropeptide Y (NPY) and substance P in axotomized dorsal root ganglia (DRGs) were examined. Self-mutilation (autotomy), a supposed pain-related behavior, was investigated after growth factor treatment. One microgram of aFGF, bFGF or NGF was applied directly to the transected sciatic nerve via a capsule. In normal rats 3.2%, 0% and 17.5% of the neuron profiles in the DRGs contained galanin-, NPY- and substance P-like immunoreactivity (LI), respectively. Sciatic nerve transection induced a distinct increase in galanin- and NPY-LIs, but a downregulation of substance P-LI. Thus three days after axotomy 23.5%, 26.9% and 9.8% of the DRG neuron profiles showed immunoreactivity for galanin-, NPY- and substance P-LI, respectively. In vivo administration of aFGF counteracted the axotomy-induced increase in galanin and NPY, whereas bFGF only suppressed NPY upregulation. NGF reversed in the injury-induced decrease in substance P-LI, but had no significant effect on galanin- and NPY-LIs. These results were confirmed by monitoring the mRNA levels for these neuropeptides. Moreover, aFGF was found to induce autotomy in 60% of the rats 3 days after axotomy. NGF produced autotomy in about 30% of the rats. Taken together, the present results suggest (1) that aFGF, bFGF and NGF differentially regulate neuropeptide expression in vivo; (2) that FGFs can inhibit neuropeptide upregulation of some peptides after nerve injury; and (3) that aFGF and NGF may induce pain-related behavior.
 ...
PMID:aFGF, bFGF and NGF differentially regulate neuropeptide expression in dorsal root ganglia after axotomy and induce autotomy. 891 73

Substance P, a putative peptide neurotransmitter contained in primary sensory neurons, is suggested to play a major role in nociceptive transmission. In the present study, the existence of substance P autoreceptor in dorsal root ganglion neurons was identified with a method we developed recently and substance P-activated inward current in the dorsal root ganglion neurons and its ionic mechanism were also explored preliminarily. The majority of the cells examined (68/76, 89.5%) were sensitive to external application of substance P (0.01-10 microM) with a concentration-dependent inward current. This current was found to result from the opening of nonselective ion channel, preferring the Na+ channel. The substance P-activated current can be suppressed by Cd2+ (0.05 microM), which suggested Ca2+ may also be involved. Soon after the neurons had been identified to be endowed with substance P receptor with whole-cell patch-clamp technique, 17 cells were chosen for immunocytochemical staining to detect substance P-immunoreactivity. Seven neurons which were classified into small and intermediate size were found to reveal substance P-immunoreactivity. Using this method we have identified the existence of substance P autoreceptor in rat DRG neurons.
 ...
PMID:Evidence for the existence of substance P autoreceptor in the membrane of rat dorsal root ganglion neurons. 947 9

The expression of neurokinin-1 receptors was studied in the fourth lumbar dorsal root ganglia of young rats using immunohistochemical and electrophysiological techniques. Use of a specific immunoserum raised against the C-terminal fragment of rat neurokinin-1 receptor revealed immunoreactivity in 32 +/- 1.5% of dorsal root ganglion neurons. The diameter of the majority of the neurokinin-1 receptor immunostained neurons was smaller than 30 microm. Double immunohistochemical labelling using neurokinin-1 receptor and substance P antibodies revealed that about 1/3 of the neurokinin-1 receptor expressing neuron contains substance P. Likewise, about 1/3 of the substance P producing DRG cells expressed the neurokinin-1 receptor. Superfusion of substance P (1 microM) to an in vitro preparation of the fourth lumbar dorsal root ganglion induced a reversible long-lasting depolarization as measured by extracellular suction electrodes attached to the dorsal roots. This response to substance P was only partially antagonized by the selective neurokinin-1 receptor antagonist RP 67580 (1 microM). Intracellular recordings distinguished between Aalpha/beta-, Adelta- and C-sub-types of ganglion neurons. Superfusion of substance P (1 microM) evoked excitatory responses in Adelta- and C-type neurons. These results demonstrate the expression of functional neurokinin-1 receptors on a subpopulation of Adelta- and C-type sensory ganglion neurons. Our data suggest the possible physiological importance of peripheral neurokinin-1 receptors located on dorsal root ganglion neurons.
 ...
PMID:Neurokinin-1 receptor expression in dorsal root ganglion neurons of young rats. 1064 95


<< Previous 1 2 3 4 5 6 Next >>