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)

The dopamine (DA)-sensitive adenylate cyclase in the substantia nigra was assayed in rats which had been subjected to 3 different kinds of brain lesion: (1) unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle; (2) unilateral lesions of the descending strio-nigral and pallido-nigral projections; (3) total lesions of the serotoninergic raphe-nigral pathway. Lesions of the medial forebrain bundle causing 97% depletion of striatal DA, 72% depletion of nigral tyrosine hydroxylase, and no change in nigral glutamate decarboxylase (GAD), resulted in no change in basal or DA-stimulated cyclic AMP production ipsilateral to the injection. Lesions of the globus pallidus, causing 70% and 79% reductions in GAD and substance P respectively in the ipsilateral nigra, produced a reduction in basal cyclic AMP production and abolished the normal increase in cyclic AMP produced by DA on the side of the lesion. Lesions to the dorsal and median raphe nuclei did not affect the normal DA-sensitive adenylate cyclase response in the nigra. The results suggest that one of the neurotransmitter functions of DA in this brain region may be to modulate the release of psi-aminobutyric acid (GABA) or substance P from synaptic terminals afferent to the nigra.
 ...
PMID:Evidence concerning the anatomical location of the dopamine stimulated adenylate cyclase in the substantia nigra. 2 89

Glutamic acid decarboxylase (GAD, EC 4.1.1.15), the enzyme which catalyzes the alpha-decarboxylation of L-glutamate to form the neurotransmitter gamma-aminobutyric acid (GABA), was localized immunocytochemically in rat neostriatum, pallidum and entopeduncular nucleus. A large amount of GAD-positive reaction product was observed in both the pallidum and entopeduncular nucleus in light microscopic preparations and was localized ultrastructurally to axon terminalis that surrounded dendrites and large somata. In the neostriatum the relative numbers of GAD-positive axons terminals per unit area were substantially less than in the pallidum. GAD-positive terminals predominantly formed symmetric synapses with somata, dendrites and spines, but a small number of them formed asymmetric synapses with either dendrites or spines. The presence of GAD within these terminals is consistent with results of other investigations which have indicated that the striatopallidal and striatoentopeduncular pathways as well as neostriatal local circuit neurons and/or collaterals from neostriatal projection neurons, use GABA as a neurotransmitter. GAD-positive reaction product was also localized within the somata and dendrites of neostriatal and pallidal neurons in colchicine-injected preparations. The GAD-positive somata in the pallidum were medium-sized neurons and since such cells project to the substantia nigra, our results are in agreement with those from other studies which demonstrate a GABAergic, pallidonigral pathway. In the neostriatum, GAD-positive somata were identified light microscopically as medium-sized neurons with either round or fusiform shapes. Electron microscopic examinations also showed GAD-positive reaction product within the perikaryal and dendritic cytoplasm of these neurons, as well as in dendritic spines. These findings are in accord with the results of studies which have indicated that medium-sized, spinous neurons of the neostriatum give rise to a GABAergic, striatonigral pathway. The significance of GAD localization within these neostriatal neurons is discussed in relation to recent findings which show that substance P is contained within this same class of striatonigral projection neuron.
 ...
PMID:The GABA neurons and their axon terminals in rat corpus striatum as demonstrated by GAD immunocytochemistry. 22 67

Immunocytochemical techniques locating neurotransmitter-synthsizing enzymes are currently being employed to determine the nature of transmitters associated with individual neurons. The use of peroxidase-anti-peroxidase Fab (PAP Fab) complex modified from Sternberger's PAP method, among several other immunocytochemical methods is recommended for the visualization of antigens in cerebral tissues. The enzyme fixed in nervous tissues is reacted with anti-enzyme produced in rabbits followed by incubation with goat-anti-rabbit serum. Subsequent application of PAP Fab complex prepared separately results in a formation of a complex composed of enzyme: anti-enzyme: goat-anti-rabbits: PAP-Fab. The enzymes can be visualized under light and electron microscope by the deposition produced by the action of peroxidase on 3,3'-diaminobenzidine. Thus, the antibody to glutamate decarboxylase (GAD), the enzyme that synthesizes gamma-aminobutyric acid (GABA) was employed to identify GABAergic neurons in central nervous system of rodents. Specific staining for GAD was highly localized in close association with synaptic vesicles in certain axon terminals including basket, Golgi and the Purkinje cell terminals in the cerebellum. The distribution of GAD observed in immunocytochemical preparations was consistent with indirect biochemical, physiological and morphological data dealing with the synaptic role of GABA neurons in the cerebellum. The correlation of the immunocytochemical distribution of GABA neurons in the spinal cord, substantia nigra, olfactory bulb, retina and Ammon's horn with physiological and biochemical results can also been obtained. The method has been successfully employed to visualize dopamine-beta-hydroxylase (DBH) and substance P. DBH, as an indicative enzyme for noradrenergic (NA) neurons, was highly localized in the neuronal soma of the locus coeruleus and in synaptic varicosities in the stria terminalis associated with synaptic vesicles. Association of substance P in probable primary afferent terminals with large vesicles also supports the synaptic function of the compound in the spinal cord.
 ...
PMID:[Immunocytochemical technique--Application for identifying GABA neurons (author's transl)]. 35 33

Following spinal cord transection there occurred decreases in Km and Vmax of glutamate decarboxylase (GAD) both above and below the lesion, and an initial decrease in the concentration of GABA. Concomitantly, there was a gradual decrease in presynaptic inhibition. Eight to 12 weeks after spinal cord transection, Km and Vmax for GAD returned to control values, but the GABA content of the spinal cord below the lesion increased significantly and presynaptic inhibition became maximally depressed. These results suggested that during the chronic phase of spinal cord injury there is a decrease in release of GABA, the interneuronal inhibitory neurotransmitter which mediates presynaptic inhibition. Diazepam, a GABA enhancer, increased presynaptic inhibition in acute and chronic spinal cats, this being accompanied by a reduction in somatic muscular spasticity. The degree of this enhancement by diazepam, however, is attenuated with gradual loss of presynaptic inhibition. In the acute cat, a conditioning volley applied to cutaneous afferents blocked the inhibition of the monosynaptic response to extensor motoneurones. In contrast, in chronic spinal cats (eight to 12 weeks), the duration of complete blockade was markedly reduced and was followed by a prolonged period which cutaneous nerve stimulation potentiated the monosynaptic discharge. Similar to GABA, there also occurred an increase of substance P below the level of the lesion. Other neurotransmitters (e.g., norepinephrine, serotonin) accumulated above and disappeared below the transection level. Although somatic msucular spasticity appears to be, to some extent, due to GABA dysfunction in the spinal cord, alterations in "normal" functioning of other neurotransmitters and the loss of supraspinal control also contribute to this state.
 ...
PMID:Correlation of changes in the GABA-ergic system with the development of spasticity in paraplegic cats. 51 79

The differential vulnerability of basal forebrain cells to ibotenate (IBO) or quisqualate (QUIS) was investigated in rats. IBO was also coinjected with cystine (CYS) or zinc (Zn). Cortical choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) activity, neurotensin receptors, and high-affinity choline uptake sites were quantified in conjunction with radioimmunoassays for neurotensin, substance P, and somatostatin; immunocytochemistry for neurotensin-, somatostatin-, Leu-enkephalin-, and ChAT-positive cells; and in situ hybridization histochemistry of somatostatin, substance P, and enkephalin mRNAs. Compared with the performance of controls, continuous alternation performance in a T maze of IBO+Zn or IBO+CYS rats was better than that of IBO rats, whereas the performance of QUIS rats was unimpaired. Of those neurotransmitter systems examined, only ChAT-immunoreactive cells were vulnerable to IBO or QUIS. However, cholinergic cell loss did not correlate with impaired performance.
 ...
PMID:Basal forebrain neurons and memory: a biochemical, histological, and behavioral study of differential vulnerability to ibotenate and quisqualate. 128 13

In order to examine the synaptic input to dopaminergic neurones in the substantia nigra from GABAergic terminals and terminals that contain substance P, double and triple immunocytochemical studies were carried out at the light and electron microscopic levels in the rat. In a first series of experiments sections of the substantia nigra were incubated to reveal axon terminals containing either substance P or glutamate decarboxylase and then incubated to reveal dopaminergic neurones using tyrosine hydroxylase immunocytochemistry. Examination of this material in the light microscope revealed that many substance P- and glutamate decarboxylase-immunoreactive boutons were associated with the dopaminergic cells. In the electron microscope it was found that the perikarya and dendrites of the dopaminergic neurons received symmetrical synaptic input from terminals that displayed immunoreactivity for substance P or glutamate decarboxylase. A small proportion of the substance P-positive boutons formed asymmetrical synapses. In a second series of experiments sections of the substantia nigra were processed by the pre-embedding immunocytochemical technique for tyrosine hydroxylase and then the post-embedding immunogold technique for gamma-aminobutyric acid (GABA). Examination in the electron microscope revealed that the tyrosine hydroxylase-positive neurons received symmetrical synaptic input from many GABA-positive terminals. Quantitative analyses demonstrated that a minimum of 50-70% of all boutons afferent to the dopaminergic neurones display glutamate decarboxylase or GABA immunoreactivity. Triple immunocytochemical studies i.e. pre-embedding immunocytochemistry for tyrosine hydroxylase and substance P, combined with post-embedding immunogold staining for GABA, revealed that some of the substance P-immunoreactive boutons that were in contact with the dopaminergic neurones also displayed GABA immunoreactivity. In a third series of experiments the combination of anterograde transport of lectin-conjugated horseradish peroxidase or biocytin with post-embedding GABA immunocytochemistry demonstrated that at least one of the sources of GABA-containing terminals in the substantia nigra is the striatum. The results of the present study: (1) demonstrate that dopaminergic neurones in the substantia nigra receive symmetrical synaptic input from GABAergic and substance P-containing terminals, (2) show that a proportion of these terminals contain both substance P and GABA and (3) suggest that the major synaptic input to dopaminergic neurones is from GABAergic terminals and that a part of this innervation is derived from the striatum.
 ...
PMID:The GABA and substance P input to dopaminergic neurones in the substantia nigra of the rat. 170 87

The expression of tachykinin-like and opioid-like peptides was studied in medium-sized neurons of the caudate nucleus in tissue from adult cats pretreated with colchicine. Two methods, a serial thin-section peroxidase-antiperoxidase technique and a two-fluorochrome single-section technique, were applied. Quantitative estimates were made mainly with the peroxidase-antiperoxidase method. The numbers of neurons expressing substance P-like, dynorphin B-like, and enkephalin-like immunoreactivity were recorded in regions identified, respectively, as striosomes and extrastriosomal matrix. Striosomes were defined by the presence of clustered substance P-positive and dynorphin B-positive neurons and neuropil. Tests for the co-existence of enkephalin-like peptide and glutamate decarboxylase-like immunoreactivity were also made with the peroxidase-antiperoxidase method. Co-expression of substance P-like and dynorphin B-like immunoreactivities was the rule both in striosomes and in the matrix. In striosomes, substance P-like immunoreactivity was found in 96% of dynorphin B-immunoreactive neurons, and in the matrix 89% of dynorphin B-positive cells contained substance P-like immunoreactivity. Substance P/dynorphin B-positive neurons corresponded to over half (57%) of the neurons in striosomes but only 39% of the neurons in the matrix. Both in the matrix and in striosomes, about two-thirds of all neurons (63% and 65%, respectively) were identified as enkephalin-positive. Among all substance P/dynorphin B-positive medium-sized neurons, 76% also contained enkephalin-like antigen. The enkephalin-positive neurons characterized by triple peptide co-existence (enkephalin/substance P/dynorphin B) represented a mean of 63% of striosomal enkephalin-positive neurons (41% of all striosomal neurons) and 35% of matrical enkephalin-positive neurons (26% of all matrical neurons). Finally, nearly all enkephalin-positive neurons were immunoreactive for glutamate decarboxylase, and therefore probably GABAergic, but only about half the glutamate decarboxylase-positive population was enkephalin-immunoreactive. These findings suggest that neuropeptides from three distinct precursors may be co-localized in single medium-sized neurons in the striatum, and that the differential patterns of co-expression of substance P-like, dynorphin B-like, and enkephalin-like peptides may confer functional specializations upon subpopulations of GABAergic neurons giving rise to the efferent projections of the striatum. The linked expression of substance P-like and dynorphin B-like peptides in single neurons both in striosomes and matrix suggests that some regulatory mechanisms controlling peptide expression apply regardless of compartment.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Co-expression of neuropeptides in the cat's striatum: an immunohistochemical study of substance P, dynorphin B and enkephalin. 170 67

The subnuclear and synaptic distribution of substance P immunoreactivity was examined in the rat interpeduncular nucleus at the light and electron microscope level. The nucleus possessed a prominent substance P-immunoreactive axonal plexus in the lateral and dorsomedial subnuclei, and in the dorsal cap of the rostral subnucleus. The density of substance P-immunoreactive axons in the remaining subnuclear divisions was sparse to moderate. Terminals of immunoreactive axons contained spherical vesicles and formed asymmetric contacts on dendritic processes exclusively. Immunoreactive neurons, restricted to the rostral subnucleus, possessed long, sparsely branched dendrites. Unlabelled terminals containing either spherical or pleomorphic vesicles contacted substance P-immunoreactive dendritic profiles. Axodendritic and axosomatic synapses containing substance P immunoreactivity pre- and postsynaptically were not observed. Ultrastructural evidence for synaptic relationships between substance P-containing profiles and those containing either choline acetyltransferase or glutamate decarboxylase was obtained by means of double antigen immunohistochemistry. Terminals of fasciculus retroflexus axons stained for choline acetyltransferase immunoreactivity formed asymmetric synaptic contacts with substance P-immunoreactive dendritic profiles. Few substance P-positive dendrites in the rostral subnucleus received terminals possessing glutamate decarboxylase activity. Unlabelled terminals containing either spherical or pleomorphic vesicles contacted substance P- and glutamate decarboxylase-immunoreactive dendritic profiles simultaneously. Terminals possessing either substance P or glutamate decarboxylase immunoreactivity formed synaptic contacts with dendritic processes of neurons in the lateral subnucleus. Many of the neurons within this subnuclear division contained glutamate decarboxylase. This study provides direct evidence of synaptic relationships between choline acetyltransferase-immunoreactive axons and substance P-immunoreactive dendritic profiles, and between substance P-positive axons and glutamate decarboxylase-immunoreactive dendrites. These findings reveal that two types of transmitter-specific axons of the fasciculus retroflexus innervate neuronal populations of the interpeduncular nucleus stained immunohistochemically for either substance P or glutamate decarboxylase.
 ...
PMID:Substance P immunoreactivity in the rat interpeduncular nucleus: synaptic interactions between substance P-positive profiles and choline acetyltransferase- or glutamate decarboxylase-immunoreactive structures. 172 Feb 26

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.
 ...
PMID:Neuropeptide changes in a primate model (Cebus apella) for tardive dyskinesia. 172 15

This study utilized the technique of in situ hybridization histochemistry to identify cells expressing neurotransmitter mRNAs in embryonic striatal tissue grafts implanted into the ibotenic acid-lesioned rat neostriatum. Synthetic 32P- or 35S-labelled oligodeoxyribonucleotide probes specific for prosomatostatin, proneuropeptide Y. proenkephalin, prodynorphin and preprotachykinin mRNAs and a 32P-labelled cRNA probe specific for glutamate decarboxylase mRNA were used to study the regional and cellular changes in these mRNA levels in the normal, lesioned and grafted neostriatum. The levels of neuropeptide Y mRNA and somatostatin mRNA were substantially increased in the striatal grafts compared with the intact control striata. The levels of glutamate decarboxylase mRNA in the grafts also appeared to be slightly elevated over those in the control striata. However, the levels of proenkephalin mRNA, prodynorphin mRNA and preprotachykinin mRNA were significantly lower in the grafts. The increased levels of neuropeptide Y mRNA and somatostatin mRNA in the grafts were due both to an increase in the number of labelled cells and to an increase in the cellular levels of each neuropeptide mRNA. In contrast, the cellular levels of proenkephalin mRNA, prodynorphin mRNA and preprotachykinin mRNA in the grafts were comparable, or elevated relative, to those in the intact striata but the density of cells expressing each of these mRNAs was reduced. Since neuropeptide Y and somatostatin are known to be present in medium to large aspiny striatal neurons (interneurons) and enkephalin, dynorphin and tachykinin peptides and GABA are localized in medium spiny striatal projection neurons, the above findings would indicate that there is a divergence in the levels of activity between these two neuronal populations in the striatal grafts. Our data suggest that the levels of gene expression and hence the functional neurotransmitter-synthesizing and releasing activity in the grafted neuron are different from those in the normal mature striatum.
 ...
PMID:Gene expression in striatal grafts--I. Cellular localization of neurotransmitter mRNAs. 197 68


1 2 3 4 5 Next >>