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)

Attempts were made to identify vestibular (VEN) and cochlear (CEN) efferent neurons in the squirrel monkey using retrograde transport of horseradish peroxidase (HRP) and immunocytochemical methods. HRP implants in the ampulla of the lateral semicircular duct retrogradely labeled cells of VEN bilaterally and some cells of CEN. VEN located lateral to the rostral part of the abducens nucleus formed a compact collection of cells, all of which were immunoreactive only to antisera for choline acetyltransferase (ChAT). CEN, identified by immunoreactivity to ChAT were located at the hilus of the lateral superior olive (LSO), along the lateral border of the LSO and sparsely near lateral parts of the ventral trapezoid nucleus (VTN). A small number of cells and fibers near the border of the VTN and lateral to the LSO were immunoreactive for leucine enkephalin (L-ENK). Fibers immunoreactive for L-ENK also were identified in the hilus of the LSO. No cells of the superior olivary complex were immunoreactive for antisera to ChAT, L-ENK, substance P, gamma-aminobutyric acid or glutamic acid decarboxylase. Cells of VEN and CEN can be identified by their immunoreactivity to ChAT, and some cells and fibers of CEN also contain L-ENK.
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PMID:Vestibular and cochlear efferent neurons in the monkey identified by immunocytochemical methods. 243 67

The rat olfactory bulb is an area displaying a particularly high density of substance P receptors in the glomerular cell layer whose functions are unknown. In pilot in vivo experiments we discovered that iontophoretically administered substance P potently depressed the spontaneous firing rate of most unidentified neurons of the rat olfactory bulb. To further elucidate the mechanism of this unexpected depressant effect, we studied the peptide's action in vitro on coronal sections of this brain region. Bath applied and microiontophoretically administered substance P depressed the spontaneous discharge of unidentified glomerular neurons in a dose-dependent fashion. This inhibiting effect is mediated indirectly via the release of another transmitter because it was abolished completely if the standard perfusion medium was replaced by a medium containing zero calcium and high magnesium. It appears that substance P acts by means of releasing GABA which in turn evokes the observed cell depression because the depressant effects were completely abolished by bath-applied bicuculline (10 microM) and picrotoxin (100 microM). In conclusion we propose that substance P indirectly depresses neuronal activity in the glomerular cell layer of the rat olfactory bulb by releasing gamma-aminobutyric acid.
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PMID:Substance P depresses neuronal activity in the rat olfactory bulb in vitro and in vivo: possible mediation via gamma-aminobutyric acid release. 244 May 22

The major input and output pathways of the mammalian striatum have been well established. Recent studies have identified a number of neurotransmitters used by these pathways as well as by striatal interneurons, and have begun to unravel their synaptic connections. The major output neurons have been identified as medium spiny neurons which contain gamma-aminobutyric acid (GABA), endogeneous opioids, and substance P. These neurons project to the pallidum and substantia nigra in a topographic and probably chemically organized manner. The major striatal afferents from the cerebral cortex, thalamus, and substantia nigra terminate, at least in part, on these striatal projection neurons. Striatal interneurons contain acetylcholine, GABA, and somatostatin plus neuropeptide Y, and appear to synapse on striatal projection neurons. In recent years, much activity has been directed to the neurochemical and hodological heterogeneities which occur at a macroscopic level in the striatum. This has led to the concept of a patch-matrix organization in the striatum.
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PMID:Neurotransmitters in the mammalian striatum: neuronal circuits and heterogeneity. 244 56

We investigated quantitative changes in markers of possible neurotransmitters in the dorsal column nuclei following transection of the dorsal column in the cat. Seven days after unilateral transection of the dorsal column at the upper cervical level, choline acetyltransferase activity and concentrations of glutamate, aspartate, gamma-aminobutyrate and substance P were measured throughout the longitudinal axis of the dorsal column nuclei. In addition, high-affinity uptake of choline, D-aspartate and gamma-aminobutyrate into the synaptosomal fraction of the dorsal column nuclei were also measured. Choline acetyltransferase activity and high-affinity choline uptake were reduced by approx. 30% on the caudal to the obex. Reduction of high-affinity uptake of D-aspartate by approx. 30% was observed on the operated side in the central part of these nuclei, although the decrease in glutamate and aspartate was not significant in the nuclei on the operated side compared with that on the intact side. No significant changes were found in the high-affinity uptake of gamma-aminobutyrate or the contents of gamma-aminobutyrate and substance P in any areas of the dorsal column nuclei. These results suggest that not only glutamate and/or aspartate but also acetylcholine may be neurotransmitter candidates for the ascending fibres terminating in the dorsal column nuclei, whereas there may be few fibres containing substance P or gamma-aminobutyrate in the dorsal column.
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PMID:Possible neurotransmitters of the dorsal column afferents: effects of dorsal column transection in the cat. 244 4

Repeated administration to rats of SCH 23390, a specific antagonist of the D-1 dopamine receptor, produced an increase in the substance P immunoreactivity in the striatum but not in the substantia nigra, whereas similar treatment with sulpiride, a specific D-2 dopamine receptor antagonist, reduced the nigral but not the striatal content of the peptide. When the two antagonists were given together, the SCH 23390-induced increase in striatal substance P was significantly reduced. The SCH 23390-induced increase in striatal substance P was curtailed by concomitant administration of progabide, a selective gamma-aminobutyric acid (GABA) receptor agonist. These results suggest the existence in the nigro-striatal complex of two different substance P-containing neurons which are differentially regulated by the dopamine receptor subtypes and indicate a role of GABA in the action of SCH 23390.
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PMID:Selective antagonists of dopamine receptor subtypes differentially affect substance P levels in the striatum and substantia nigra. 244 3

In the present study, the activation of the nociceptive dorsal horn neurons in rats by iontophoretic substance P (SP) has been observed. Thus, the role of SP in spinal nociception is further identified. In addition, the inhibitory effects of iontophoretic SP on nociceptive response (C response) of dorsal horn neurons can also be observed even in rats that have undergone dorsal half transection of spinal cord. These inhibitory effects can be partially blocked by pretreatment with iontophoretic bicuculline but not by naloxone. It indicates that the SP-induced inhibitory effects on the nociceptive response may be mainly mediated by the presynaptic inhibition in which gamma-aminobutyric acid (GABA) may be involved. In view of the fact that the inhibitory effect of stimulation of nucleus raphe magnus (NRM) on the nociceptive response of dorsal horn neurons in rats depleted of 5-HT with parachlorophenylalanine (pCPA) can be significantly blocked by iontophoretic SP-antagonist, it is supposed that SP may be involved in descending modulation on spinal pain transmission.
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PMID:Dual action of substance P in nociception and pain modulation at spinal level. 245 Dec 86

The effects of intranigral injection of gamma-aminobutyric acid (GABA) (dose range: 10.0-300.0 nmol), dynorphin A (0.005-0.5 nmol) and substance P (0.00007-7.0 nmol) on striatal dopamine (DA) release, and dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) formation were studied by microdialysis. It was found that both GABA and dynorphin A produced a dose-dependent decrease in the release of striatal DA following injection into the ipsilateral substantia nigra, the pars reticulata. In contrast, intranigral injection of substance P produced an increase in DA release. However, the dose-response curve for the substance P effect had a biphasic shape. The maximum effect was produced by 0.007 nmol, whereas higher doses (0.07-0.7 nmol) produced less pronounced effects. At the highest dose (7.0 nmol), substance P produced a strong decrease of DA release. Striatal levels of DOPAC and HVA were enhanced by GABA, dynorphin A and substance P. The present results support the concept that substance P, directly or indirectly, provides a positive feed-back regulation for the release of striatal DA, whereas GABA and dynorphin exert a negative feed-back regulation.
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PMID:Differential modulation of striatal dopamine release by intranigral injection of gamma-aminobutyric acid (GABA), dynorphin A and substance P. 245 97

Substance P and gamma-aminobutyric acid (GABA) were colocalized by immunocytochemistry in two subpopulations of amacrine cells in the cat retina. All of the cells which stained for substance P also showed GABA reactivity. However, there were many GABA-immunoreactive cells which did not stain for substance P. The presence of neuropeptides provides a basis for additional neurochemical characterization of the multiple populations of GABA immunoreactive cells.
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PMID:Colocalization of substance P and gamma-aminobutyric acid in amacrine cells of the cat retina. 245 1

To assess the roles of substance P in neurologic or psychiatric illnesses, effects of acute or chronic (40- or 80-day dietary) treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content were investigated in the rat brain. Either acute or chronic trihexyphenidyl administration did not alter substance P content when administered alone and did not prevent the haloperidol-induced substance P decrease in the striatum and substantia nigra when coadministered with haloperidol. Chronic dietary carbamazepine administration dose-dependently increased substance P content in the striatum and substantia nigra, but not in the raphe area, in a haloperidol-reversible manner. Carbamazepine also dose-dependently increased gamma-aminobutyric acid levels in the substantia nigra without altering the striatal dopamine turnover rate. The lack of effect of trihexyphenidyl, an anticholinergic drug used to treat antipsychotic drug-induced extrapyramidal (Parkinson) syndromes, suggests that antipsychotic drug-induced reduction in substance P content is not involved in the extrapyramidal side effects. Since the effects of carbamazepine on substance P content are identical with previously described effects of lithium, an alteration in substance P neurotransmission may be one of the neurochemical bases of common clinical and behavioral effects of carbamazepine and lithium on affective disorders.
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PMID:Effects of chronic treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content in rat brain: a possible implication of substance P in affective disorders. 245 42

1. The pharmacological profile of Spantide, [D-Arg1, D-Trp7,9, Leu11] substance P, as a substance P (SP) antagonist was examined in isolated spinal cords of newborn rats. Potential changes were recorded extracellularly from a lumbar ventral root (L1-L5). Application of SP to the perfusion bath with a brief pressure pulse of 0.05-0.8 s duration produced a dose-dependent depolarization of the ventral root. Spantide in concentrations of 2-16 microM depressed the depolarizing responses of the ventral root to SP in a concentration-dependent manner. The log dose-response curve of SP was shifted to the right in the presence of 16 microM-Spantide by log 5. The responses to neurokinin A (NKA) and bombesin were similarly depressed by 16 microM-Spantide whereas the responses to noradrenaline, gamma-aminobutyric acid (GABA), neurotensin and thyrotrophin-releasing hormone were not affected by 16 microM-Spantide. 2. In an isolated spinal cord-tail preparation of the newborn rat, brief pulse injection of capsaicin into the perfusion solution of the tail induced a depolarizing response in a lumbar ventral root (L3-L5). This response probably represents a nociceptive C fibre reflex. 3. The capsaicin-induced nociceptive reflex was markedly depressed by 16 microM-Spantide and the reflex recovered its original amplitude and shape 30-60 min after removal of Spantide. 4. The capsaicin-induced nociceptive reflex was depressed by morphine (2 microM) and dynorphin (1-13) (0.2 microM), and these effects were reversed by 1 microM-naloxone. 5. In an isolated spinal cord preparation of the newborn rat, stimulation of a dorsal root with single or double shocks induced depolarizing responses of slow time course in both ipsilateral and contralateral ventral roots of the same segment. These slow depolarizing responses were also depressed by 16 microM-Spantide. In contrast the monosynaptic reflex was not affected by 16 microM-Spantide. 6. The present results suggest that SP and NKA are involved as neurotransmitters in the capsaicin-induced nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat.
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PMID:Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat. 245 77


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