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

Sympathetic preganglionic neurons (SPN) in rat spinal cord were activated by the reflex stimulation of bulbospinal sympathetic neuronal pathways after a nitroprusside-induced hypotension. Hypotension-sensitive SPN, identified by immunoreactivity (IR) to the product of the immediate early gene c-fos and to choline acetyltransferase, were localized in the intermediolateral cell column of thoracic and upper lumbar cord, particularly middle to lower thoracic cord. Putative neurotransmitters, or their markers, in varicose fiber networks around SPN were identified. Nearly all hypotension-sensitive (Fos-IR) SPN were apposed by varicose fibers immunoreactive for tyrosine hydroxylase, serotonin, substance P, or enkephalin. Neuropeptide Y (NPY)- or phenylethanolamine-N-methyl transferase (PNMT)-IR varicose fibers apposed Fos-IR SPN in the upper and middle thoracic spinal cord, but in lower thoracic segments some Fos-IR SPN lacked these appositions. In thoracic segment 12, 51% +/- 5% of Fos-IR SPN (n = 9 rats) lacked PNMT contacts and 25% +/- 3% of Fos-IR SPN (n = 8 rats) lacked NPY contacts. In contrast to other chemically defined afferents, galanin-IR varicose fibers apposed fewer than half of the Fos-IR SPN in the middle to lower thoracic cord. Neurotransmitters/neuromodulators that might influence the activity of SPN acting in the baroreflex-mediated control of blood pressure have been identified. Uniformity in the neurochemistry of some fibers making connections with Fos-IR SPN, regardless of their segmental origin, suggests that common sets of neurons provide convergent inputs to all hypotension-sensitive SPN. Other fibers show topographic differences in their contacts with Fos-IR SPN, suggesting that subgroups of hypotension-sensitive SPN are targeted by particular neuron groups.
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PMID:Neurochemistry of nerve fibers apposing sympathetic preganglionic neurons activated by sustained hypotension. 1211 67

The role of neurokinin 1 (NK(1)) receptor and possible interaction between NK(1) and N-methyl-D-aspartic acid (NMDA) glutamatergic receptors were investigated on spinal c-fos expression after lower urinary tract irritation with acetic acid infusion in rats. At both levels of the first (L(1)) and sixth lumbar (L(6)) spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals project, respectively, the selective NK(1) receptor antagonist CP-99,994 dose dependently reduced the total number of c-fos protein (Fos)-positive cells. However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for NK(1) receptor, did not have any effect on the total number of Fos-positive cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor antagonist (MK-801), either of which alone did not affect c-fos expression, significantly inhibited c-fos expression at both levels of the spinal cord. Regarding regional differences, the number of Fos-positive cells decreased significantly at all regions of the L(6) level, but only at the dorsal horn of the L(1) level. These results indicate that NK(1) receptor is involved in spinal c-fos expression after lower urinary tract irritation and that NK(1) and NMDA receptors have a synergistic interaction in the spinal processing of nociceptive input from the lower urinary tract.
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PMID:NK(1) receptor and its interaction with NMDA receptor in spinal c-fos expression after lower urinary tract irritation. 1218 90

Dopamine (DA) and glutamate neurotransmission is thought to be critical for psychostimulant drugs to induce immediate early genes (IEGs) in the caudate-putamen (CPu). We report here, however, that the ability of DA and glutamate NMDA receptor antagonists to attenuate amphetamine-evoked c-fos mRNA expression in the CPu depends on environmental context. When given in the home cage, amphetamine induced c-fos mRNA expression predominately in preprodynorphin and preprotachykinin mRNA-containing neurons (Dyn-SP+ cells) in the CPu. In this condition, all of the D1R, D2R and NMDAR antagonists tested dose-dependently decreased c-fos expression in Dyn-SP+ cells. When given in a novel environment, amphetamine induced c-fos mRNA in both Dyn-SP+ and preproenkephalin mRNA-containing neurons (Enk+ cells). In this condition, D1R and non-selective NMDAR antagonists dose-dependently decreased c-fos expression in Dyn-SP+ cells, but neither D2R nor NR2B-selective NMDAR antagonists had no effect. Furthermore, amphetamine-evoked c-fos expression in Enk+ cells was most sensitive to DAR and NMDAR antagonism; the lowest dose of every antagonist tested significantly decreased c-fos expression only in these cells. Finally, novelty-stress also induced c-fos expression in both Dyn-SP+ and Enk+ cells, and this was relatively resistant to all but D1R antagonists. We suggest that the mechanism(s) by which amphetamine evokes c-fos expression in the CPu varies depending on the stimulus (amphetamine vs. stress), the striatal cell population engaged (Dyn-SP+ vs. Enk+ cells), and environmental context (home vs. novel cage).
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PMID:Amphetamine-evoked c-fos mRNA expression in the caudate-putamen: the effects of DA and NMDA receptor antagonists vary as a function of neuronal phenotype and environmental context. 1280 22

The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types. The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions. In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity. Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized. Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity. The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release. The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems. The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A. In these studies, botulinum toxin type A was found to block the release of glutamate. Furthermore, Fos, a product of the immediate early gene, c-fos, expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin. These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways. Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine.
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PMID:Evidence for antinociceptive activity of botulinum toxin type A in pain management. 1288 89

Methylphenidate is a psychostimulant which inhibits the dopamine transporter and produces dopamine overflow in the striatum, similar to the effects of cocaine. Excessive dopamine action is often associated with changes in gene expression in dopamine-receptive neurons. Little is known about methylphenidate's effects on gene regulation. We investigated whether a methylphenidate treatment regimen known to produce behavioural changes would alter gene expression in the striatum. Using in situ hybridization histochemistry, we assessed the effects of acute and repeated methylphenidate treatment on the expression of immediate-early genes (c-fos, zif 268) and neuropeptides (dynorphin, substance P, enkephalin) in adolescent rats. Acute methylphenidate treatment (0-10 mg/kg, i.p.) produced a dose-dependent increase in the expression of c-fos and zif 268. These effects were most pronounced in the dorsal striatum at middle to caudal striatal levels, and were found for doses as low as 2 mg/kg. Repeated treatment with methylphenidate (10 mg/kg/day, 7 days) increased the expression of dynorphin, which was highly correlated with the acute immediate-early gene response across different striatal regions. Moreover, after repeated methylphenidate treatment, cocaine-induced expression of c-fos and zif 268, as well as of substance P, was significantly attenuated throughout the striatum. These effects of repeated methylphenidate treatment mirror those produced by repeated treatment with cocaine or other psychostimulants and are considered to reflect drug-induced neuroadaptations. Thus, our findings demonstrate that acute and repeated methylphenidate treatment can produce molecular alterations similar to other psychostimulants.
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PMID:Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum. 1451 37

This study utilized anatomical and behavioral-pharmacological methods to determine the role of NK(1)-Substance P receptors in the midbrain periaqueductal gray (PAG) in defensive rage behavior in cats. For behavioral pharmacological experiments, monopolar stimulating electrodes were implanted in the medial hypothalamus for elicitation of defensive rage behavior and cannula-electrodes were implanted in the PAG for microinjections of receptor compounds. Microinjections of the NMDA antagonist, AP-7 (2 nmol), into the dorsal PAG blocked defensive rage elicited by medial hypothalamic stimulation, thus establishing the PAG as a synaptic region that receives hypothalamic inputs linked to defensive rage behavior. Microinjections of the NK(1) agonist, GR73632, into the same injection sites facilitated defensive rage in a dose-dependent manner, and also induced spontaneous hissing in five cats. The effects of GR73632 were reduced by pretreatment of the PAG with the NK(1) antagonist, GR82334 (16 nmol), microinjected into the same sites. Microinjections of GR73632 (8 nmol) into the PAG also suppressed predatory attack elicited by stimulation of the lateral hypothalamus. Immunohistochemical methods utilized to detect Substance P and Fos immunoreactivity revealed that neurons in the PAG activated after defensive rage-inducing medial hypothalamic stimulation lie in the same region as Substance-P-immunoreactive processes. Fos immunoreactivity was highest in the dorsomedial aspect of the rostral PAG after medial hypothalamic stimulation. Cats that were unstimulated or that exhibited predatory attack after lateral hypothalamic stimulation had low c-fos expression levels in the PAG. Substance P immunoreactivity was high throughout the dorsal PAG. The results indicate that NK(1) receptors in the PAG potentiate defensive rage and suppress predatory aggression in the cat.
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PMID:Differential effects of NK1 receptors in the midbrain periaqueductal gray upon defensive rage and predatory attack in the cat. 1464 48

Substance P (SP) is considered to be involved in the regulation of respiration, in particular when respiratory demands are increased, such as during hypoxic stress. In the present study we have investigated the effects of intracerebroventricular pre-treatment with the selective NK-1 receptor antagonist RP67580 on the respiratory response to hypoxia in 5-day-old rat pups. Basal respiration was not altered by RP67580. When subjected to hypoxia (10% O(2)), rat pups pre-treated with RP67580 were unable to sustain the increased respiratory frequency at 10 min. In situ hybridisation demonstrated increased expression of c-fos mRNA in several brainstem areas following hypoxia. This activation was blocked by the antagonist in the retrotrapezoid nucleus and the rostral ventrolateral medulla, areas known to be involved in the hypoxic ventilatory response. This study corroborates a role of endogenously released SP, mediated via NK-1 receptors, in the sustained response to hypoxia in 5-day-old rat pups and suggests that neurons in the rostral ventrolateral medulla are important in this function. It also represents a further example that neuropeptides are released under stressful conditions.
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PMID:Hypoxic response in newborn rat is attenuated by neurokinin-1 receptor blockade. 1510 25

Spinal neurones that receive inputs from primary afferent fibres and have axons projecting supraspinally to the medulla oblongata may represent a pathway through which nociceptive and non-nociceptive peripheral stimuli are able to modulate cardiorespiratory reflexes. Expression of the neurokinin-1 (NK1) receptor is believed to be an indicator of lamina I cells that receive nociceptive inputs from substance P releasing afferents, and similarly, sst2A receptor expression may be a marker for neurones receiving somatostatinergic inputs. In this study, immunoreactivity for these two receptors was investigated in rat spinal neurones retrogradely labelled by injections of cholera toxin B or Fluorogold into the nucleus of the solitary tract (NTS). In addition, nociceptive activation of these labelled cells was studied by immunodetection of Fos protein in response to cutaneous and visceral noxious chemical stimuli. NK1 and sst2A receptors in lamina I were localised to mainly separate populations of retrogradely labelled cells with fusiform, flattened and pyramidal morphologies. Examples of projection neurones expressing both receptors were, however observed. With visceral stimulation, many retrogradely labelled cells expressing c-fos were immunoreactive for the NK1 receptor, and a smaller population was sst2A positive. In contrast, with cutaneous stimulation, only NK1 positive retrogradely labelled cells showed c-fos expression. These data provide evidence that lamina I neurones receiving noxious cutaneous and visceral stimuli via NK1 receptor activation project to NTS and so may be involved in coordinating nociceptive and cardiorespiratory responses. Moreover, a subpopulation of projection neurones that respond to visceral stimuli may receive somatostatinergic inputs of peripheral, local or supraspinal origins.
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PMID:Substance P (NK1) and somatostatin (sst2A) receptor immunoreactivity in NTS-projecting rat dorsal horn neurones activated by nociceptive afferent input. 1526 32

The effect of substance P (Sub P) injected intrathecally (i.t.) on c-fos mRNA expression in various tissues was examined in the present study. We found that a single administration of Sub P (0.5 nM) caused an increase of the c-fos mRNA level in the hypothalamic-pituitary-adrenal (HPA) axis, hippocampus, and spinal cord. The time-course study showed that c-fos mRNA level was maximal at 10 min and began to decrease 30 min after the Sub P injection in all tissues, and the Sub P-induced increase of the c-fos mRNA level was returned to the control level 1 h after the injection. The kinetics of the c-fos mRNA expression in mice that were repeatedly injected with Sub P (every 30 min interval up to 4 times) were different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA level in the hypothalamus and the spinal cord induced by i.t. injected Sub P remained at a high level. In the pituitary gland, adrenal gland, and hippocampus, the increased level of c-fos mRNA expression gradually returned to the control level during the repeated substance P injections up to 4 times. Our results suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA expression in the spinal cord, hippocampus, and HPA axis. In mice repeatedly injected with Sub P, the kinetics of c-fos mRNA appear to be different varied from tissue to tissue.
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PMID:Alterations of c-Fos mRNA expression in hypothalamic-pituitary-adrenal axis and various brain regions induced by intrathecal single and repeated substance P administrations in mice. 1546 Apr 49

Dopamine action alters gene regulation in striatal neurons. Methylphenidate increases extracellular levels of dopamine. We investigated the effects of acute methylphenidate treatment on gene expression in the striatum of adult rats. Molecular changes were mapped in 23 striatal sectors mostly defined by their predominant cortical inputs in order to determine the functional domains affected. Acute administration of 5 and 10 mg/kg (i.p.) of methylphenidate produced robust increases in the expression of the transcription factor c-fos and the neuropeptide substance P. Borderline effects were found with 2 mg/kg, but not with 0.5 mg/kg. For 5 mg/kg, c-fos mRNA levels peaked at 40 min and returned to baseline by 3 h after injection, while substance P mRNA levels peaked at 40-60 min and were back near control levels by 24 h. These molecular changes occurred in most sectors of the caudate-putamen, but were maximal in dorsal sectors that receive sensorimotor and medial agranular cortical inputs, on middle to caudal levels. In rostral and ventral striatal sectors, changes in c-fos and substance P expression were weaker or absent. No effects were seen in the nucleus accumbens, with the exception of c-fos induction in the lateral part of the shell. In contrast to c-fos and substance P, acute methylphenidate treatment had minimal effects on the opioid peptides dynorphin and enkephalin. These results demonstrate that acute methylphenidate alters the expression of c-fos and substance P preferentially in the sensorimotor striatum. These molecular changes are similar, but not identical, to those produced by other psychostimulants.
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PMID:Topography of methylphenidate (ritalin)-induced gene regulation in the striatum: differential effects on c-fos, substance P and opioid peptides. 1563 41


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