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 effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Striato-nigral dynorphin and substance P pathways in the rat. I. Biochemical and immunohistochemical studies. 242 58

We have developed a dissociated primary cell culture of noradrenergic neurons from the locus ceruleus of postnatal (1- to 5-d-old) mice or rats. Slices of the brain stem were made on a Vibratome. Then the region of locus ceruleus, which was identified by observing the slices under a dissecting microscope, was dissected out from the slices. The removed fragments of brain slices were dissociated and cultured up to 3 weeks on a non-neuronal feeder layer, which consisted predominantly of astroglial cells, or on a fibronectin-treated collagen substratum. After 2 weeks of culture, about 70% of total neuronlike cells revealed positive catecholamine histofluorescence, indicating that they were probably noradrenergic neurons. About 98% of large- and medium-sized cultured neurons (soma diameter greater than or equal to 20 microns) was histofluorescence positive. The fluorescence-positive cells had long processes rich in varicosities, and the shape of their soma was either multipolar or fusiform. Electron microscopy using permanganate fixation revealed that the varicosities along their processes had small granular vesicles, which may contain norepinephrine. Physiological properties of these noradrenergic neurons were investigated with intracellular microelectrodes or with the whole-cell version of the patch clamp. We observed that many cells were producing spontaneous firing. Many of these spontaneously firing cells had no obvious contact with neighboring cells. The neurons were depolarized when glutamate was applied by pressure ejection. They also responded to GABA and glycine with either hyperpolarization or depolarization, and these responses were antagonized by picrotoxin and strychnine. Application of substance P generally produced depolarization with an increase in input resistance. The neurons responded with hyperpolarization to somatostatin, beta-endorphin, and enkephalin. This culture system will become a useful tool for elucidating the cellular and molecular properties of the central noradrenergic neurons.
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PMID:Noradrenergic neurons from the locus ceruleus in dissociated cell culture: culture methods, morphology, and electrophysiology. 243 74

Experiments reported in this study have been performed in order to investigate cholinergic and GABA-ergic neurotransmitter systems and substance P in the realization of internal inhibition and pain reinforcement. This was accomplished during the elaboration of inhibitory and defensive conditioned reflexes to light flashes in alert, nonimmobilized rabbits. Present results together with a review of past research indicate that the cholinergic system is directly involved in transmitting the effects of pain reinforcement to neocortical neurons. Substance P, a neuropeptide, reduces the background activity of neocortical and hippocampal neurons and the response of cortical neurons to pain and positive conditioned stimuli. The cholinergic system and substance P exert a modulating effect on the elaboration of internal inhibition. Phenybut, a GABA derivative capable of penetrating the blood-brain barrier, enhances inhibitory hyperpolarization in the cerebral cortex and improves discrimination between the inhibitory and reinforcing light flashes. It appears, therefore, that the GABA-ergic system plays a leading part in the elaboration of internal inhibition. Neuronal activity and slow potential changes in response to positive conditioned and pain stimuli occur in the same direction after administering the preparations, and the dynamics of these changes is different from that in responses to inhibitory stimuli. It may be supposed on these grounds that the neurotransmitter and neuromodulator systems studied possess a considerable degree of plasticity.
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PMID:On neurotransmitter mechanisms of reinforcement and internal inhibition. 243 77

The influence of GABA-ergic stimulation on the centrally evoked pressor and tachycardic responses to substance P (SP) was investigated in conscious rats. Intracerebroventricular (i.c.v.) pretreatment with the potent GABA agonist muscimol attenuated the pressor responses to i.c.v. administered SP in a dose-dependent and reversible fashion. Inhibition was maximal 5-60 min after muscimol injection and lasted up to 3 h. In contrast, the increases in heart rate in response to i.c.v. administered SP were not consistently inhibited by muscimol. Central pretreatment with muscimol prevented the increase of plasma adrenaline but not of plasma noradrenaline in response to i.c.v. administered SP. Our results demonstrate that the GABA-ergic system can exert an inhibitory control on pathways mediating the central pressor actions of SP. The selective inhibition of adrenaline secretion by muscimol implies that suppression of sympathetic outflow to the adrenal gland may be involved as an important mechanism. In addition, our findings point to a dissociation between pathways mediating the pressor and tachycardic effects of SP.
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PMID:The central pressor actions of substance P are inhibited by GABA. 243 40

Neurotensin-like immunoreactivity (NT-LI) was demonstrated in projection neurons of the striatum and nucleus accumbens in the cat by combining immunohistochemistry and the fluorescent retrograde neuronal labeling method. In colchicine-treated cats, many neurons with NT-LI were found in the caudate nucleus, nucleus accumbens, and putamen. Most of these neurons were medium-sized neurons with spiny dendrites. NT-LI of neuronal elements in the caudate nucleus and nucleus accumbens formed dense aggregates with irregular figures, which appeared to correspond to the striosomes of Graybiel et al. (Proc. Natl. Acad. Sci. USA 75:5723-5726, '78; Exp. Brain Res. 34:189-195, '79; Neuroscience 6:377-397, '81). Fibers with NT-LI were distributed massively to the globus pallidus and ventral midbrain regions, but not to the entopeduncular nucleus. In the ventral midbrain regions, many fine varicose fibers with NT-LI were distributed to the pars compacta and pars lateralis of the substantia nigra, ventral tegmental area, and retrorubral area. In the pars reticulata of the substantia nigra, however, fibers with NT-LI were rather sparse. Examination of consecutive sections immunostained for NT, enkephalin (Enk), GABA, and substance P (SP) revealed that 50% of neurons with NT-LI in the caudate nucleus and nucleus accumbens exhibited Enk-LI, 15% showed GABA-LI, and 5% manifested both Enk-LI and GABA-LI; no NT-positive neurons in the striatum and nucleus accumbens showed SP-LI. No morphological differences were found between NT-positive neurons with Enk-LI and/or GABA-LI and those without Enk-LI and GABA-LI. Most neurons with NT-LI in the striatum and nucleus accumbens were retrogradely labeled with True Blue injected into the globus pallidus, pars compacta and pars lateralis of the substantia nigra, and ventral tegmental area. After hemitransection severing neuronal connections between the ventral midbrain regions and the forebrain structures, fibers with NT-LI and those with Enk-LI in the ventral midbrain regions were markedly reduced in number.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotensin in projection neurons of the striatum and nucleus accumbens, with reference to coexistence with enkephalin and GABA: an immunohistochemical study in the cat. 243 69

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

An isolated spinal cord-tail preparation of the newborn rat was developed and used for studying the effects of various drugs. The cord and the tail were separately perfused with oxygenated artificial cerebrospinal fluid. Application of capsaicin in a small amount to the tail induced a depolarizing response of the lumbar ventral root (L3-L5) lasting for about 30 sec. The stimulating action of capsaicin was potentiated by previous perfusion of the tail with a medium containing prostaglandin E1 or E2. The capsaicin-induced nociceptive reflex was depressed by application to the spinal cord of morphine, Met-enkephalin, dynorphin (1-13), somatostatin, adenosine, GABA and a substance P (SP) antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP, and potentiated by bicuculline. The present preparation will be useful for the future studies on pain and analgesic drugs.
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PMID:Effect of a substance P antagonist on capsaicin-induced nociceptive reflex in the isolated spinal cord-tail preparation of the rat. 244 68

A variety of neurotransmitters have been implicated in the pathophysiology of chorea as exemplified by Huntington's chorea. These include dopamine, serotonin, acetylcholine, GABA and a variety of neuropeptides including substance P and somatostatin. Despite biochemical data that suggests that alterations in other neurotransmitters may be of greater significance, pharmacologic data still supports a major role of dopamine in the actual clinical manifestation of chorea.
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PMID:Chorea. 244 58

The neurokinins, physalaemin, substance P, neurokinin A and bradykinin, were tested on the responses of single spinal neurons to the purines, adenosine 5'-triphosphate (ATP) and adenosine 5'-monophosphate and to GABA. Experiments were done on anaesthetized cats, recording extracellularly from functionally identified sensory neurons in the lumbar dorsal horn. All compounds were administered by iontophoresis. Neurokinins caused a slow, prolonged excitation which outlasted the period of application. Physalaemin was tested on responses to ATP in 24 units. In each case application of ATP caused either depression, excitation or a biphasic response when the application was not pre-conditioned by ejection of physalaemin. For 11 units, with ATP applications subthreshold to alter the on-going firing rate, such applications caused depression when they were preceded by administration of physalaemin. Three units were tested with ATP applications which caused the excitatory response; when the applications of ATP were preceded by ejection of physalaemin, there was then a depressant component in the response. In these 14 cases, the magnitude of the depression or of the depressant component of the response, was measured using currents which failed to produce depression in the absence of physalaemin ejection; the mean magnitude of this depression was 34.7 +/- 1.6% (+/- S.E.M.). With the 10 remaining units, responses to ATP were unaffected by application of physalaemin. The early components of the biphasic and excitatory responses were unaffected by physalaemin and hence it appeared to have a differential effect, enhancing only the depressant effects of ATP. The enhancement of depression was reversible, lasting up to 30 min following a single ejection. Neither control current nor glutamate mimicked the effect of physalaemin in the responses to application of ATP. The depressant response to adenosine 5'-monophosphate was also enhanced by physalaemin: ejections of adenosine 5'-monophosphate subthreshold to affect the on-going firing rate caused depression after physalaemin application in 3 of 8 units (average depression: 35.0 +/- 3.3%). On the other hand, depression induced by GABA was unaffected by physalaemin in every case (n = 8); in 4 of these cases GABA was tested on units for which purine-induced depression was enhanced by physalaemin. Thus, physalaemin preferentially affected depressant responses to ATP and to adenosine 5'-monophosphate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purine-induced depression of dorsal horn neurons in the cat spinal cord: enhancement by tachykinins. 244 38

gamma-Aminobutyric acid (GABA), substance P and dopamine concentrations and choline acetyltransferase (ChAT) activity were measured in post-mortem cerebrocortical and basal ganglial areas of 14 controls and 4 patients with pathologically verified Pick's disease (1 classic case and 3 cases of the generalized form). GABA and substance P levels in the substantia nigra and the globus pallidus were generally decreased, corresponding to the moderate to severe loss of small neurones in the striatum. ChAT activities in the striatum varied from case to case, in proportion to various degrees of loss of large neurones in the striatum. These neurotransmitter abnormalities in Pick's disease were exactly the same as those in Huntington's disease. However, dopamine concentrations were markedly reduced in the striatum in Pick's disease, whereas striatal dopamine in Huntington's disease is reported to be increased. A dopamine reduction in the striatum of Pick's disease was more disproportionately prominent than expected for various degrees of nigral cell loss. This may be one of the important factors which prevents the generation of choreic movements in Pick's disease in spite of definite striatal atrophy similar to Huntington's disease.
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PMID:Studies on neurotransmitter markers of the basal ganglia in Pick's disease, with special reference to dopamine reduction. 245 Jan 80


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