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)

Rats were exposed to short-term restraint (held by the tail for 1 min), injected s.c. with saline or subjected to the combination of these treatments. Fifteen and 30 min after these treatments the means serum corticosterone level was significantly increased by more than four times, compared to rats taken directly from their home cages, indicating a stress response. In the peri-aqueductal grey, the level of substance P-like immunoreactivity was increased by 45% (P < 0.01) and 65% (P < 0.01) 30 and 60 min after the combined treatment, respectively. Significant increases of the level of substance P-like immunoreactivity in the peri-aqueductal grey were also found after restraint only and after a s.c. saline injection. Similar, but less marked, changes in the level of cholecystokinin-like immunoreactivity in the PAG were also seen. In the accumbens a significantly decreased level of substance P-like immunoreactivity was encountered at 15 and 30 min after treatment, while the levels of cholecystokinin- and neuropeptide Y-like immunoreactivity were not significantly changed. In other regions studied, no effects on peptide levels were seen. The changes in peptide levels had a time course similar to that of the increase in serum corticosterone. Also the successive removal of rats from a common cage was found to increase significantly the serum corticosterone and the substance P-like immunoreactivity in the peri-aqueductal grey in the animals that were taken late in sequence from the cage.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Short-term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri-aqueductal grey and limbic regions of rat brain. 128 65

The purpose of this study is to observe the effect of intracerebroventricular (icv) and intra-PAG injection of substance P (SP) on serotonin (5-HT) contents of hypothalamus, hippocampus, striatum and its relation with the change of pain threshold, electroacupuncture (EA) analgesia. The results were as follows: (1) After icv injection of SP, the pain threshold and the 5-HT contents of hypothalamus, hippocampus were significantly increased. After depletion of the 5-HT contents in brain by pCPA, the inhibitor of 5-HT synthesis, the effect of SP on elevating pain threshold and the 5-HT contents of hypothalamus, hippocampus were markedly attenuated, bud did not prevent the analgesic effect of SP (2) The pain threshold and the 5-HT contents of hypothalamus, hippocampus were dose-dependently increased by intra-PAG injection of SP. (3) The intra-PAG injection of SP introduced simultaneously with high or low frequency EA did not affect the change of 5-HT contents of three brain regions, but caused a more marked elevation of pain threshold. These results suggest that the serotoninergic system may be activated by PAG for the mediation of SP induced analgesia. There is a synergic action of analgesia between the effects produced by intra-PAG injection of SP and those by high or low frequency EA.
 ...
PMID:[Effect of intracerebral injection of substance P on serotonin contents of several brain regions and its relation with pain threshold, electroacupuncture analgesia in rats]. 171 75

Previous studies have demonstrated an antinociceptive effect of brain-derived neurotrophic factor (BDNF) following infusion into the midbrain, near the periaqueductal grey and dorsal raphe nuclei. BDNF administration attenuated the behavioural response in the tail-flick and hot-plate tests, two models employing a phasic, thermal high-intensity nociceptive stimulus; the present studies extend our previous findings to include a model of moderate, continuous pain resulting from a chemical stimulus, the formalin test. Midbrain infusion of BDNF decreased the behavioural paw flinch response to subcutaneous formalin injection in both the early and late phases of the test. As our previous studies showed that BDNF-induced analgesia was reversible by naloxone, we have examined the effects of BDNF administration on brain and spinal cord levels of neuropeptides involved in the modulation of nociceptive information, including the endogenous opioid peptides, met-enkephalin and beta-endorphin, as well as substance P and neuropeptide Y (NPY). At the site of infusion, within the PAG and dorsal raphe, BDNF increased the level of beta-endorphin by 63%, but had no effect on substance P, metenkephalin or NPY levels. In the dorsal spinal cord, substance P (113% increase), beta-endorphin (97% increase) and NPY (64% increase) were elevated, although ventral spinal cord levels of these peptides remained unchanged. These studies demonstrate a modulatory effect of BDNF on relevant neuropeptides within areas of the brain and spinal cord involved in the processing of nociceptive information.
 ...
PMID:BDNF produces analgesia in the formalin test and modifies neuropeptide levels in rat brain and spinal cord areas associated with nociception. 762 Jun 17

The experiments described in this review reveal that the expression and modulation of aggressive responses in the cat are organized by two distinct sets of pathways. One set of pathways is associated with the elicitation of a specific form of attack behavior. It includes the medial hypothalamus and its projections to the PAG for the expression of defensive rage behavior and the lateral hypothalamus and its descending projections for the expression of predatory attack behavior. The primary focus of the present review is upon the analysis of defensive rage behavior. It was demonstrated that the pathway from the medial hypothalamus to the PAG, which appears to be essential for elicitation of defensive rage, is powerfully excitatory and utilizes excitatory amino acids that act upon NMDA receptors within the PAG. The other pathways examined in this review arise from different nuclei of the amygdala and are modulatory in nature. Here, two facilitatory systems have been identified. The first involves a projection system from the basal complex of amygdala that projects directly to the PAG. Its excitatory effects are manifest through excitatory amino acids that act upon NMDA receptors within the PAG. The second facilitatory pathway arises from the medial nucleus of the amygdala. However, its projection system is directed to the medial hypothalamus rather than the PAG. Its neurotransmitter appears to be substance P that acts upon NK1 receptors within the medial hypothalamus (see Figure 10). It has yet to be determined whether substance P acts upon any of the other neurokinin receptor subtypes. It should also be pointed out that the substance P pathway from the medial amygdala to the medial hypothalamus functions to suppress predatory attack behavior elicited from the lateral hypothalamus. In this network, it is likely that the modulatory effects of the medial amygdala require the presence of a second, inhibitory pathway from the medial hypothalamus that innervates the lateral hypothalamus. At the present time, the neurochemical nature of this second pathway remains unknown, although it is suggested that such neurons may be GABAergic. One major inhibitory pathway was also identified. It arises principally from the central nucleus of the amygdala and projects to the PAG. Its powerful suppressive effects upon PAG elicited defensive rage behavior are mediated through opioid peptides that act upon mu receptors within the PAG. While the present series of studies have begun to define the structural and functional nature of the neural systems that regulate aggressive behavior, our understanding of the overall mechanisms regulating different forms of aggressive behavior remains incomplete.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neurotransmitters regulating feline aggressive behavior. 763 40

The objective of this study was to document, through comprehensive means, normal distribution and concentration of catecholamines in various regions of the CNS of pigs, an increasingly popular animal model used for transgenic manipulation of neural genes. The effects of gonadal steroidal status on this distribution were also assessed by comparing CNS catecholamine concentrations among mature male pigs (boars), immature (gilts) and mature female pigs (sows), and adult male pigs castrated prepuberally (barrows). Dissected tissue samples from the CNS were extracted in 2 N acetic acid, filtered through a 0.2 micron filter, then quantitated by reverse-phase high performance liquid chromatography using a C-18 reverse phase column with electrochemical detection. In both boars and sows the highest concentrations of norepinephrine (NE) were found in the diencephalic areas and brain stem. Gilts exhibited elevated concentrations of NE in the olfactory bulbs (OB), hypothalamus, pons, and corpus trapezoideum-locus ceruleus (LC) compared to lower concentrations in corresponding areas of sows. Prepuberal castration of the male was associated with significantly lower NE concentrations in the striatum, periaqueductal area (PAG), pons, LC, and spinal cord. The sow exhibited significantly lower NE concentrations in the mammillary area (Mam), PAG, pons, and spinal cord than those in corresponding areas of the boar. Dopamine concentrations appeared to be similar in all areas of the brain and spinal cord studied in the sow and boar. Results demonstrated that prepuberal castration of the male appears to significantly alter the DA content of the Mam and dorsal spinal cord, in contrast to gilts who possess significantly higher concentrations of DA. It is concluded from our studies that in general, catecholamine concentrations in various regions of the brain and spinal cord of sexually mature pigs parallel distributions of neuropeptides, substance P, and methionine enkephalin, as previously reported. In addition, significant association was found between gonadal activity and catecholamine concentrations in discrete areas of the pig brain.
 ...
PMID:Distribution of catecholamines in the central nervous system of the pig. 837 8

Evidence is reviewed concerning the brain areas and neurotransmitters involved in aggressive behavior in the cat and rodent. In the cat, two distinct neural circuits involving the hypothalamus and PAG subserve two different kinds of aggression: defensive rage and predatory (quiet-biting) attack. The roles played by the neurotransmitters serotonin, GABA, glutamate, opioids, cholecystokinin, substance P, norepinephrine, dopamine, and acetylcholine in the modulation and expression of aggression are discussed. For the rat, a single area, largely coincident with the intermediate hypothalamic area, is crucial for the expression of attack; variations in the rat attack response in natural settings are due largely to environmental variables. Experimental evidence emphasizing the roles of serotonin and GABA in modulating hypothalamically evoked attack in the rat is discussed. It is concluded that significant progress has been made concerning our knowledge of the circuitry underlying the neural basis of aggression. Although new and important insights have been made concerning neurotransmitter regulation of aggressive behavior, wide gaps in our knowledge remain.
 ...
PMID:Neuropharmacology of brain-stimulation-evoked aggression. 998 25

The transneuronal tracer, pseudorabies virus (PRV), was used to identify pathways from the uterine cervix which may be involved in induction of analgesia and abbreviation of estrus by vaginocervical stimulation. In Experiment I, PRV immunoreactivity (PRV-IR) in brain and spinal cord was examined 3-5 days after injection into the cervix of ovariectomized (OVX) female rats given estrogen (E) or control treatments. No differences in viral labeling were observed between OVX and OVX+E females at any time. PRV-infected cells were observed to increase as a function of time and at progressively higher CNS levels. PRV-IR neurons were first observed on day 3 post-infection at L6 in the SPN. Increased labeling was observed at day 4 in the SPN and the DGC at L6 and S1 spinal segments. Dorsal horn neurons showed PRV-IR by 4.5 days. Five days post-infection, labeling was seen in the IML and lamina X in T12-L1 segments, and in medullary raphe, A5, nPGi, nGi, DMV, lateral reticular, Barrington's nuclei, and in the midbrain PAG. In Experiment II, the effects of bilateral L6 dorsal root rhizotomy (RH) combined with unilateral (UPx) or bilateral (BPx) pelvic nerve transection on PRV infectivity were examined 5 days after infection. Despite reductions in substance P labeling in the dorsal horn following RH, PRV-IR neurons persisted in this area. In RH+UPx females, labeling persisted bilaterally in the SPN and DGC at L6. RH+BPx almost completely eliminated the PRV labeling in L6 and S1. Horizontal sections showed distinct patterns of infectivity within the IML of thoracolumbar and SPN of lumbosacral segments consistent with infection in the hypogastric and pelvic nerves, respectively. Our data indicate that retrograde transport of PRV occurs via the hypogastric and pelvic nerves after injection of the virus into the uterine cervix. Furthermore, significant intraspinal processing is likely to occur between thoracolumbar and lumbosacral levels in the modulation of reproductive tract function.
 ...
PMID:Pseudorabies virus tracing of neural pathways between the uterine cervix and CNS: effects of survival time, estrogen treatment, rhizotomy, and pelvic nerve transection. 1071 75

1. Violence and aggression are major public health problems. 2. The authors have used techniques of electrical brain stimulation, anatomical-immunohistochemical techniques, and behavioral pharmacology to investigate the neural systems and circuits underlying aggressive behavior in the cat. 3. The medial hypothalamus and midbrain periaqueductal gray are the most important structures mediating defensive rage behavior, and the perifornical lateral hypothalamus clearly mediates predatory attack behavior. The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area, cingulate gyrus, and prefrontal cortex project to these structures directly or indirectly and thus can modulate the intensity of attack and rage. 4. Evidence suggests that several neurotransmitters facilitate defensive rage within the PAG and medial hypothalamus, including glutamate, Substance P, and cholecystokinin, and that opioid peptides suppress it; these effects usually depend on the subtype of receptor that is activated. 5. A key recent discovery was a GABAergic projection that may underlie the often-observed reciprocally inhibitory relationship between these two forms of aggression. 6. Recently, Substance P has come under scrutiny as a possible key neurotransmitter involved in defensive rage, and the mechanism by which it plays a role in aggression and rage is under investigation. 7. It is hoped that this line of research will provide a better understanding of the neural mechanisms and substrates regulating aggression and rage and thus establish a rational basis for treatment of disorders associated with these forms of aggression.
 ...
PMID:Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression. 1126 61

Electrophysiological properties, reaction to substance P (SP) receptor agonist, and co-existence of glutamate (Glu) and SP in neurons of the spinal dorsal root ganglion (DRG) of the rat were investigated in vitro. The main results were: (1) According to the fiber conduction velocity, totally 135 intracellularly recorded DRG neurons were divided into A alpha/beta type (> 12 m/s) and C type (< 1.3 m/s). There were remarkable differences between the fast after hyperpolarization (fAHP) of action potential between the two types: fAHP of C type neurons had smaller amplititude and longer duration, whereas the fAHP of A alpha/beta type neurons had larger amplititude and shorter duration. (2) Among 22 DRG neurons of which overshoots of action potential appeared, specific SP receptor agonist Sar-SP induced depolorization in 42% (5/12) of the A alpha/beta type neurons and 80% (8/10) of the C type neurons. (3) Biocytin was intracellularly injected into the 22 Sar-SP administrated DRG neurons. After fixation and section, employing the immunofluorescent histochemical multi-staining technique for phosphate-activated glutaminase (PAG, a specific marker for glutamatergic neurons), SP and biocytin, 25% (3/12) of the A alpha/beta type neurons and 80% (8/10) of the C type neurons showed both PAG- and SP-like immunoreactivities. There was a great difference between the percentages of the PAG/SP co-existing A alpha/beta type neurons and C type neurons (P < 0.05). The present results indicated that there were some differences in chemicoanatomical and electrophysiological properties between A alpha/beta type and C type neurons, and SP might facilitate the discharge of DRG neurons through activating SP autoreceptors on their membrane.
 ...
PMID:[Co-existence of glutamate and substance P in electrophysiologically identified dorsal root ganglion neurons of rats]. 1132 57

Hydrogen sulphide (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS). We have earlier shown that H(2)S acts as a mediator of inflammation. However the mechanism remains unclear. In this study, we investigated the presence of H(2)S and the expression of H(2)S synthesizing enzymes, CSE and CBS, in isolated mouse pancreatic acini. Pancreatic acinar cells from mice were incubated with or without caerulein (10(-7) M for 30 and 60 min). Caerulein increased the levels of H(2)S and CSE mRNA expression while CBS mRNA expression was decreased. In addition, cells pre-treated with DL-propargylglycine (PAG, 3 mM), a CSE inhibitor, reduced the formation of H(2)S in caerulein treated cells, suggesting that CSE may be the main enzyme involved in H(2)S formation in mouse acinar cells. Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue caerulein-treated acinar cells. Inhibition of endogenous production of H(2)S by PAG significantly suppressed SP concentration, PPT-A expression and NK1-R expression in the acini. To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (NaHS), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of PPT-A and NK1-R in acinar cells. These results suggest that the pro-inflammatory effect of H(2)S may be mediated by SP-NK-1R related pathway in mouse pancreatic acinar cells.
 ...
PMID:Hydrogen sulfide acts as a mediator of inflammation in acute pancreatitis: in vitro studies using isolated mouse pancreatic acinar cells. 1748 80


1