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)

The effects of intrathecal administration of neurokinin A, substance P and [Tyr5, D-Trp6,8,9 Arg10]neurokinin A-(4-10) (Men 10207), a specific NK-2 receptor antagonist, on the spinal nociceptive flexor reflex were studied in decerebrate, spinalized, unanesthetized rats. Intrathecal neurokinin A and substance P facilitate the flexor reflex in a similar manner. The reflex facilitation to intrathecal neurokinin A, but not substance P, is dose-dependently blocked by pretreatment with Men 10207. The NK-2 receptor antagonist by itself facilitates the flexor reflex with a potency about 10 times less than that of neurokinin A, indicating a partial agonistic property. Reversible depression of the flexor reflex, which is not due to nonspecific spinal blockade, is observed after 700 pmol Men 10207. Further increasing the dose of Men 10207 to 7 nmol for 20 s at an intensity that activates unmyelinated (C) fibers stimulation of peripheral nerves at 1 Hz for 20 s at an intensity that activates unmyelinated (C) fibers facilitates the ipsilateral flexor reflex. The duration of the facilitation after conditioning stimulation of the cutaneous sural nerve is several minutes and about 1 h after conditioning stimulation of the gastrocnemius muscle nerves. Pretreatment with Men 10207 (70-700 pmol) has no effect on facilitation by the sural nerve conditioning stimulation, but effectively blocks the long-term reflex facilitation to the gastrocnemius nerve stimulation. The present results indicate a distinct role for NK-2 tachykinin receptors in mediation of spinal reflex excitability in the rat. Neurokinin A may be involved in the long-term increase of spinal reflex excitability after activation of unmyelinated fibers innervating muscle.
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PMID:On the role of NK-2 tachykinin receptors in the mediation of spinal reflex excitability in the rat. 171 50

Tardive dyskinesia has been connected with regional reductions of GABA functions in the basal ganglia. In view of the possibility that peptides are involved in neuroleptic-induced dyskinesias substance P and dynorphin A levels were measured in the basal ganglia of the Cebus apella model for tardive dyskinesia. In addition, regional glutamate decarboxylase activities, dopamine, homovanillic acid and dihydroxyphenylacetic acid levels were monitored. A significant dyskinesia-related decrease in glutamate decarboxylase activity was found in the subthalamic nucleus, the medial segment of globus pallidus and the rostral part of substantia nigra in accordance with earlier findings. Cebus monkeys with an intact GABA system (neuroleptic-treated controls without dyskinesia) showed increased levels of substance P and homovanillic acid in the caudate nucleus. The changes were confined to the caudal part of the body of the caudate and the nucleus accumbens. On the other hand, the dyskinetic monkeys, with a defective GABA system, did not demonstrate a similar substance P rise in the caudate or nucleus accumbens, but showed a depression of homovanillic acid levels in the caudal part of the body of the caudate nucleus. Dynorphin A, dopamine and dihydroxyphenylacetic acid showed no dyskinesia-related changes. In conclusion, the difference in glutamate decarboxylase activity between animals developing dyskinetic symptoms vs those who did not, was reflected by regional changes in substance P and homovanillic acid levels.
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PMID:Neuropeptide changes in a primate model (Cebus apella) for tardive dyskinesia. 172 15

Recent immunohistochemical studies have shown the distribution of histaminergic neurons in the mammalian brain, which are concentrated in the tuberomammillary nucleus of the posterior hypothalamus and project efferent fibers to almost all parts of the brain from the olfactory bulb to the spinal cord. Histaminergic neurons co-express other neuroactive substances, such as gamma-aminobutyric acid, adenosine, substance P, galanin and Met-enkephalin-Arg-Phe. In addition, pharmacological studies have demonstrated the presence of presynaptic histamine H3-receptors (autoreceptor) in addition to H1- and H2-receptors. The specific agonist (alpha-methylhistamine) and antagonist (thioperamide) of H3-receptors were developed. Results from a number of studies indicate a variety of physiological roles of neuronal histamine such as thermoregulation, feeding behavior, sexual activity, sleep-wakefulness cycle, hormonal regulation and so on. Moreover, histaminergic drugs affect not only the emotional behavior, but also are effective to treat some patients of depression, Parkinson's disease, akathisia, motion sickness and so on. The central histaminergic neuron system is also affected by mental disorders and neuropsychopharmacological drugs. This review especially focused on these points and suggests that the central histaminergic neuron system may play an important role in the regulation of mental functions.
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PMID:[Recent advances in neuropsychopharmacology of the central histaminergic neuron system]. 192 57

We have examined the effect of perivascular denervation on the ability of acetylcholine to produce endothelium-dependent relaxation in the isolated perfused mesenteric arterial bed. Treatment with capsaicin prevented the development of substance P and calcitonin gene-related peptide containing perivascular nerve fibres. Treatment with 6-hydroxydopamine prevented the development of catecholaminergic perivascular nerve fibres. In the arterial beds from capsaicin treated rats there was a depression of the ability of Acetylcholine to produce endothelium dependent relaxation. No change in endothelium-dependent relaxation to ACh was found in 6-hydroxydopamine treated rats.
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PMID:The effect of perivascular denervation on endothelium-dependent relaxation to acetylcholine. 211 55

The activity levels of a dynorphin converting enzyme (DCE), a substance P endopeptidase (SPE) and a substance P alpha-amidating enzyme (SP-GLYE) were measured in the cerebrospinal fluid (CSF) of 90 patients with chronic low back pain, sciatica and neurological signs of rhizopathy. The DCE activity was significantly higher in men than in women. Age was related to the DCE activity independent of sex, i.e., older patients had higher enzyme activity. The activities of two substance P converting enzymes were not related to sex or age. Self-reported pain experience and affective covariates (anxiety, depression, hostility, somatization) of pain, and myelography data were not found to be related to the enzyme activity levels once adjustment had been made for sex and age. The activity levels of the enzymes measured here had no predictive value for the long-term outcome of rehabilitation and therapy at the 5-year follow-up of the patients. The sex difference in DCE activity provides further evidence in favor of the role of gender in the psychoendocrine coping with pain distress.
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PMID:Neuropeptide converting enzyme activities in CSF of low back pain patients. 215 Aug 78

1. We have compared the ability of various tachykinins and selective tachykinin receptor agonists to induce contraction of the endothelium-denuded rabbit pulmonary artery (RPA) and hamster trachea (HT) and have estimated the affinity of some newly developed NK2 selective antagonists in the same tissues. 2. In confirmation of previous findings, experiments with the agonists indicated that NK2 receptors are the main if not the sole mediators of the response to tachykinins in both RPA and HT. No evidence for significant degradation of neurokinin A (NKA) was found in either tissue when experiments were repeated in the presence of a mixture of peptidase inhibitors (thiorphan, captopril and bestatin, 1 microM each). 3. The peptide antagonists tested were: Peptide I = [Tyr5, D-Trp6,8,9, Arg10]-NKA(4-10); Peptide II = [Tyr5, D-Trp6,8,9, Arg10]-NKA(3-10); Peptide III = Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2. The three peptides produced a concentration-dependent rightward shift of the concentration-response curve to NKA in both RPA and HT with no significant depression of the maximal response attainable. The slopes of the Schild plots were not significantly different from unity, indicating a competitive antagonism. Peptides I and II were about 100 times more potent in the RPA than in the HT, while Peptide III was about 100 times more potent in the HT than RPA. 4. The pA2 values obtained in these two tissues with the three antagonists were not significantly different when tested in the absence or presence of peptidase inhibitors, or when a selective NK2 receptor agonist, [beta Ala8]-NKA(4-10) was used instead of NKA. Similar pA2 values were obtained after 15 or 90min of incubation with the antagonists. Peptides I, II and III had no inhibitory effect on contractions produced by noradrenaline in the RPA or by carbachol in the HT. 5. Peptides I, II and III showed weak or no antagonistic activity toward the vasodilatator effect of substance P in the dog carotid artery (NK, receptor-mediated) or toward the contractile effect of neurokinin B in the rat portal vein (NK3 receptor-mediated). 6. These results provide pharmacological evidence for heterogeneity of NK2 receptors in the RPA and HT. The NK2 receptors present in these tissues are not discriminated by natural tachykinins or selective agonists, but are recognized with very different affinity by NK2 receptor antagonists.
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PMID:Competitive antagonists discriminate between NK2 tachykinin receptor subtypes. 216 37

The effects of methionine enkephalin (ME) and substance P (SP) were tested on the chemosensory discharge of the cat carotid body-nerve preparation in vitro. ME superfused in concentrations of 10(-8) to 10(-5) M depressed the sensory discharge, an effect followed by receptor excitation (rebound). Bolus applications of ME (30 ng to 3.0 microgram) induced variable effects (excitation or depression) on the discharge, excitation being more pronounced with the smaller doses. Superfusions with SP (10(-8) to 10(-5) M) either excited or depressed the discharge, excitation being more pronounced with higher SP concentrations (i.e. 10(-6) M). Bolus applications of SP (43 ng to 0.5 micrograms) also excited or depressed the sensory discharge. These variations may be dose-dependent. Superfused ME (10(-6) M) significantly depressed the chemoreceptor response to hypoxia (100% N2) and hypercapnia (6% CO2, pH 7.43). The responses to NaCN and acidity (pH 6.0) were marginally depressed. Superfused SP (10(-6) M) clearly depressed the responses to hypoxia, those to hypercapnia and NaCN were marginally affected but the effects of acidity were not altered. When the peptides were tested against the receptor responses to exogenously applied putative neurotransmitters (ACh, dopamine--DA), it was found that ME tended to depress both the ACh and DA actions whereas SP (10(-6) M) tended to increase their effects. Superfusions with naloxone (10(-6) M) increased the basal chemosensory discharge and this enkephalin blocker partially relieved the depressant effect of ME on the ACh-induced response. It is concluded that carotid body chemoreceptors have excitatory and inhibitory reactive sites to both ME and SP although their precise location is still unknown.
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PMID:Effects of methionine-enkephalin and substance P on the chemosensory discharge of the cat carotid body. 241 43

Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum. Presynaptic nerves were excited by a focal stimulating electrode on an interganglionic strand. Fast excitatory postsynaptic potentials (e.p.s.ps) were depressed in amplitude by morphine and [Met5]enkephalin in the concentration range of 1 nM-1 microM. Nicotinic depolarizations evoked by exogenously applied acetylcholine (ACh) were not affected by these opioids. Hyperpolarization of the presynaptic fibres probably contributed to the depression of the fast e.p.s.p. because fast e.p.s.ps evoked by low stimulus voltages were more depressed than those evoked by high stimulus voltages and fast e.p.s.ps resulting from activation of a single presynaptic fibre were blocked in a non-graded manner. Opioids depressed the slow e.p.s.p. in those neurones in which they did not change the resting membrane potential. The slow e.p.s.p. was increased in amplitude in those neurones hyperpolarized by opioids. Depolarizations resulting from application of barium, substance P or ACh were also enhanced by opioids. Equivalent circuit models in which opioids increase, and substance P or ACh decrease, the same potassium conductance could account for this enhancement. The actions of opioids were prevented or reversed by naloxone (1 nM-1 microM). It is concluded that morphine and enkephalin inhibit the release of ACh and a non-cholinergic transmitter from fibres of the myenteric plexus, and that this may involve a hyperpolarization of presynaptic fibres. Additionally, opioids can interact postsynaptically with other substances which affect membrane potassium conductances.
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PMID:Opioid inhibition of synaptic transmission in the guinea-pig myenteric plexus. 241 22

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothane-anesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaCO2 equal to and PaO2 greater than vehicle injected controls. In addition, the minute ventilation-PaCO2 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaCO2 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent. The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaCO2 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaCO2 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin. These results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.
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PMID:Altered respiratory response to substance P in capsaicin-treated rats. 241 26

A topographic map of the substance P and monoamine neurons in the ventrolateral medulla of the cat has been constructed from peroxidase anti-peroxidase immunohistochemically stained sections. The coordinates of this map use the foramen cecum of the medulla oblongata (i.e. the triangular depression at the junction between the caudal boundary of the pons and the rostral limit of the median fissure between the pyramidal tracts) as the zero point. Two distinct groups of substance P neurons have been found: a rostral group lies ventral to the facial nucleus and a caudal one is found ventrolateral to the inferior olivary nucleus. Two dopamine beta-hydroxylase-containing cell groups were identified that correspond to the A1 and A5 cell groups. The A5 cell group lies dorsal, lateral and caudal to superior olivary nucleus. The A1 cell group lies approximately 4.0-5.0 mm lateral to the midline at the level of the inferior olive; these cells lie mainly dorsolateral to the region of the magnocellular division of the lateral reticular nucleus. The B1 and B3 serotonin (5-hydroxytryptamine) cell groups of the ventrolateral medulla appear to form a continuous column with a rostral and a caudal swelling. The rostral group begins at the level of the facial nucleus (approximately 4 mm caudal to the foramen cecum) and is concentrated in the area just lateral to the pyramidal tract. It becomes reduced in size approximately 8.0 mm caudal to the foramen cecum, and then enlarges to form a caudal group (approximately 10 mm caudal to foramen cecum). Portions of this column overlap with the caudal substance P cell group. The C1 cell group lies in a restricted zone approximately 4.0 mm lateral to the midline at the level of the rostral part of the inferior olivary nucleus.
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PMID:Topographic organization of substance P and monoamine cells in the ventral medulla of the cat. 241 70


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