Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

WIN 64821 (1) is a substance P (SP) antagonist isolated from a fungal culture (Aspergillus sp., SC319). It is a symmetrical dimer biosynthesized from four aromatic amino acid molecules: each equivalent half of the dimer is constructed from one molecule of phenylalanine (Phe) and one molecule of tryptophan (Trp). Feeding analogs of Phe, Trp, and other amino acids to intact cells of SC319 has yielded 36 biosynthetic analogs of WIN 64821. The analogs fall into three categories: substitutions on the indoline ring, substitutions on the Phe-derived phenyl ring, and replacement of the phenyl ring by an aliphatic group. In addition, these directed biosynthesis experiments generated asymmetrical dimers (derived from three amino acids) and, often, symmetrical dimers (derived from two amino acids). The relative SP binding affinities of several analogs suggest involvement of both the indoline and phenyl moieties in SP receptor binding.
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PMID:WIN 64821, a novel neurokinin antagonist produced by an Aspergillus sp. III. Biosynthetic analogs. 751 39

Anatomical relationships between tachykinin-containing terminals and neurons of the medial preoptic area that innervate the arcuate nucleus were studied using silver staining of the retrograde tracer wheat germ agglutinin-apoperoxidase-gold (WGA-ApoHRP-gold) complex injected in the arcuate nucleus and pre-embedding immunocytochemistry for neurokinin A (NKA). At the histological level, retrogradely labeled cells not stained for NKA were seen to be surrounded by numerous NKA-immunopositive punctate profiles, in particular in the dorsal part of the medial preoptic area. At the ultrastructural level, retrogradely labeled cell bodies and dendritic profiles displayed highly electron-dense silver particle accumulations over the cytoplasm. The were seen in synaptic contact with one or several NKA-immunoreactive axon terminals containing small clear vesicles and dense-cored vesicles. Such synapses were either symmetrical or asymmetrical. The occurrence of synaptic contacts between tachykinin terminals and cells innervating the arcuate nucleus in the medial preoptic region provides a morphological support for a tachykinergic regulation of preoptic afferences to the arcuate nucleus. These results suggest that tachykinins are implicated in the indirect control of neuronal activity in the arcuate nucleus notably via the preoptic area. Consequently, tachykinins are potentially able to regulate indirectly numerous neuroendocrine events involving the tuberoinfundibular system.
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PMID:Tachykinergic synaptic inputs to neurons of the medial preoptic region which project to the rat arcuate nucleus. 751 35

Neurophysiological and pharmacological evidence suggests that glutamate, gamma-aminobutyric acid and tachykinins (substance P and neurokinin A) each have a role in cardiovascular regulation in the nucleus tractus solitarii. This study describes the ultrastructural relationships between nerve terminals immunoreactive for these substances in the nucleus tractus solitarii of the cat using post-embedding immunogold (single and double) labelling techniques on sections of tissue embedded in LR White resin. The technique combines a high specificity of labelling with good ultrastructural and antigenic preservation. Glutamate-immunoreactive terminals, recognized by their high density of gold particle labelling compared to the mean tissue level of labelling, accounted for about 40% of all synaptic terminals in the region of the nucleus tractus solitarii analysed (medial, dorsal, interstitial, gelatinosus and dorsolateral subnuclei). They appeared to comprise several morphological types, but formed mainly asymmetrical synapses, most often with dendrites of varying size, and contained spherical clear vesicles together with fewer dense-cored vesicles. Substance P- and neurokinin A-immunoreactive terminals were fewer in number (9% of all terminals) but similar in appearance, with the immunoreaction restricted to the dense-cored vesicles. Analysis of serial- and double-labelled sections showed a co-existence of substance P and neurokinin A-immunoreactivity in 21% of glutamate-immunoreactive terminals. Immunoreactivity for gamma-aminobutyric acid was found in 33% of all terminals in the nucleus tractus solitarii. These predominantly contained pleomorphic vesicles and formed symmetrical synapses on dendrites and somata. Possible sites of axo-axonic contact by gamma-aminobutyric acid-immunoreactive terminals onto glutamate-or tachykinin-immunoreactive terminals were rare, but examples of adjacent glutamate and gamma-aminobutyric acid-immunoreactive terminals synapsing on the same dendritic profile were frequent. These results provide an anatomical basis for a gamma-aminobutyric acid mediated inhibition of glutamatergic excitatory inputs to the nucleus tractus solitarii at a post-synaptic level.
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PMID:Glutamate, gamma-aminobutyric acid and tachykinin-immunoreactive synapses in the cat nucleus tractus solitarii. 776 1

The suprachiasmatic nucleus (SCN) in the hypothalamus controls many of the circadian rhythms in mammalian species. In the present study, we investigated the location of substance P receptor (SPR)-containing neurons in the rat SCN, using a specific antibody against SPR, which corresponds to the NK-1 subtype of tachykinin receptors, and also examined the synaptic relationship between SPR-containing neurons and retinal fibers at the ultrastructural level. An SPR-immunoreactive meshwork of labeled somata and dendrites was identified in the SCN. The strongest SPR-immunoreactivity was observed in the dorsal and lateral parts of the SCN. Many labeled somata were identified there and their dendrites protruded ventrally from their somata. A few SPR-immunoreactive somata were observed also in the ventral part of the SCN and within the optic tract. In the SCN of eye-enucleated animals, degenerating retinal fibers were shown to terminate on SPR-immunoreactive dendrites forming asymmetrical axo-dendritic contacts.
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PMID:A relationship between substance P receptor and retinal fibers in the rat suprachiasmatic nucleus. 858 3

Our previous studies have proved the presence of substantial amounts of peptidergic nerve fibers in the anterior pituitary of human, monkey, dog, and rat, and synaptic contacts have been demonstrated on corticotrophs and somatotrophs in the dog. The present study is aimed at investigating the synaptic relationship between axons and gland cells in the rat. The substance P-like-immunoreactive nerve fibers were studied immuno-electron-microscopically. They were nonmyelinated and varicose. Typical synaptic contacts between the fibers and every type of the hormone-secreting gland cell could be identified, most frequently on lactotrophs. No synaptic contacts were found on the folliculo-stellate cell. The synaptic contacts were of asymmetrical type with clusters of small round clear vesicles at the presynaptic site and scattered large dense-cored vesicles. This pattern of synaptic relationships was markedly different from that in the dog. The presence of synapses in the anterior pituitary of the rat implies a direct neural regulation of certain cells and strongly supports our hypothesis of neural-humoral dual regulation of this gland.
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PMID:Synaptic relationship of substance P-like-immunoreactive nerve fibers with gland cells of the anterior pituitary in the rat. 876 59

The tachykinin peptide innervation of the developing dorsal lateral geniculate nucleus of the rabbit was studied with immunocytochemical techniques at the light and electron microscopic levels by using an antibody directed to the C-terminal of the mammalian tachykinin peptides. At birth, the rabbit's lateral geniculate nucleus was densely innervated by a large number of labeled fibers. These relatively unbranched axons were dispersed throughout the nucleus but showed a higher density of fiber packing in the external layer of the alpha sector. Over the next three weeks this pattern of distribution changed dramatically. Immunoreactive fibers were gradually eliminated from most of the nucleus, and, by the end of the third postnatal week, they appeared as a narrow plexus deep to the optic tract. At the same time, these axons showed major morphological alterations as they gradually became thicker and developed terminal arborizations characterized by spherical or elongated enlargements. Overall, by the end of the third postnatal week, the pattern of distribution and appearance of tachykinin-labelled fibers in the dorsal lateral geniculate nucleus were similar to those described in the adult rabbit (Brecha et al., 1987). Ultrastructural analysis has shown that during the first week, tachykinin-immunoreactive profiles appeared as round or elongated varicosities making asymmetrical synapses with dendritic shafts throughout the lateral geniculate nucleus. Thereafter, as they were progressively restricted to the external layer of the alpha sector of the nucleus, they began to form multiple synaptic contacts with neuronal processes in complex glomerular neuropil. On the basis of the present and previous findings, we suggest that tachykinin peptides not only play a role as putative neurotransmitters in the retinogeniculate pathway, but they may also play a role in the development of the lateral geniculate nucleus and of the retinogeniculate projection system in the rabbit.
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PMID:Transient features of tachykinin peptide innervation of the dorsal lateral geniculate nucleus of the rabbit during postnatal development. 908 15

In order to examine the morphological substrates for neuronal connections between neuronal elements of the coeliac-mesenteric ganglion containing immunoreactivity (IR) for tyrosine hydroxylase (TH) and substance P (SP), a double-immunostaining was performed. The first antigen to SP was labelled with gold-substituted silver-intensified peroxidase, which results in a granular gold deposit of high electron and light opacity. The second antigen was the TH labelled with peroxidase and a diaminobenzidine chromogen without silver-gold particles. About of 85% of the neurons contained TH immunoreactivity in the coeliac-mesenteric ganglia. The SP IR nerve fibres were mostly found around the principal ganglion cells throughout the ganglion. In most cases they made direct synaptic contact with TH positive nerve cells and dendrites. These SP-IR boutons were also found in synaptic contact with other non-labelled postsynaptic terminals and with the soma. SP-IR nerve terminals establish both symmetrical and asymmetrical synaptic contacts with TH-IR nerve elements. Some of the nerve cells which ware TH positive, were also labelled for SP. TH positive boutons were also observed in synaptic contact with other TH-IR perikarya and dendrites. Our results suggest that SP may play an important role for the integrative activities of the ganglion with regard to gastrointestinal functions.
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PMID:Electron microscopic immunocytochemical evidence for the synaptic connections between tyrosine hydroxylase and substance P containing nerve elements in the coeliac ganglion of cat revealed by a double labelling technique. 912 85

Large neurons outlined with numerous substance P (SP)-like immunoreactive (LI) boutons were detected immunocytochemically in the dorsal horn of the chicken spinal cord at the light microscopic level. The cervical enlargement was mainly used for observations. By electron microscopy, asymmetrical synapses were observed between the SP-LI axon terminals and the soma and dendrites of the large neurons. Cell bodies of the large neurons were mostly localized in the lamina I and the region lateral to the lamina I. Some of the cell bodies were also located in the lamina II. Their dendrites extended in the lamina I, in the region lateral to the lamina I, and deeply in the lamina II. In the lamina II, dendrites of these neurons formed synapses with SP-containing central terminals in synaptic glomeruli known to originate from primary afferents. The findings suggest that these large neurons receive nociceptive information directly from primary afferents. In the light of previous investigations, these neurons are considered to be pain-transmitting long ascending tract neurons.
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PMID:Large dorsal horn neurons which receive inputs from numerous substance P-like immunoreactive axon terminals in the laminae I and II of the chicken spinal cord. 922 Apr 71

Synaptic contacts between noradrenaline (NA) neurons and GABA (gamma-aminobutyric acid) afferents and/or substance P (SP) afferents in the locus coeruleus (LC) were examined by a combination of immunoelectron microscopic mirror method and double-immunostaining method. For visualization of NA and GABA, we used antibodies against NA and GABA synthesizing enzymes, i.e., tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD). GAD-immunoreactive (IR) and SP-IR axon terminals often made synaptic contacts with NA neurons, respectively. Furthermore, we identified that a single NA neuron simultaneously receives synaptic inputs from GAD-IR and SP-IR afferents. These NA neurons made symmetrical synaptic contacts with GAD-IR axon terminals and asymmetrical contacts with SP-IR axon terminals. This suggests that central NA neuronal mechanisms are affected by GABA and SP neurons in a different manner.
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PMID:GABA-ergic and substance P-ergic double-innervation to noradrenergic neurons in the rat locus coeruleus. 930 37

The present study determined the effects of intraventricularly administered glial cell line-derived neurotrophic factor on the behavioral and neurochemical sequelae of unilateral excitotoxic lesions of the striatum. Distinct asymmetrical rotational behavior in response to peripheral administration of amphetamine (5 mg/kg) was noted one and two weeks following injections of quinolinic acid (200 nmol) into two sites in the left striatum. In rats given a single intraventricular injection of glial cell line-derived neurotrophic factor (10-1000 micrograms) 30 min before the toxin, amphetamine-induced rotational behavior was significantly attenuated. Analysis of Nissl-stained coronal sections showed marked neuronal loss in the striatum ipsilateral to the quinolinic acid injections, which was at least partially prevented by glial cell line-derived neurotrophic factor D1 and D2 dopamine binding sites in the striatum, the majority of which are localized to subpopulations of GABAergic neurons, were decreased to a similar extent by quinolinic acid. Moreover, the reduction was attenuated by glial cell line-derived neurotrophic factor treatment to a similar degree, suggesting that the two subpopulations of GABAergic striatal output neurons are equally vulnerable to excitotoxic damage. Concomitant changes in neurotransmitter function as a result of the lesion were also observed: [3H]GABA uptake into striatal target tissues (globus pallidus and substantia nigra) was considerably reduced in the lesioned compared to the contralateral unlesioned tissues, as were [3H]choline and [3H]dopamine uptake into striatal synaptosomes. Similarly, striatal choline acetyltransferase activity was decreased by the lesion. Decrements in neuropeptide levels of similar magnitude were evident ipsilateral to the lesion; substance P, met-enkephalin and dynorphin A contents in the globus pallidus and substantia nigra were significantly reduced. Striatal somatostatin and neuropeptide Y levels were not altered. All of the neurochemical deficits induced by striatal quinolinic acid lesions were attenuated by intraventricular delivery of glial cell line-derived neurotrophic factor. Continuous intraventricular infusion of this trophic factor (10 micrograms/day) over a two-week period did not afford notable improvement compared to the single injection of 10 micrograms. In contrast, continuous infusion of brain-derived neurotrophic factor (10 micrograms/day) directly into the striatum did not affect any of the neurochemical parameters studied. However, neurotrophin-3 (10 micrograms/day) delivery into the striatum significantly increased [3H]GABA uptake, but only modestly affected [3H]choline uptake. The results indicate that glial cell line-derived neurotrophic factor counteracts neuronal damage induced by a striatal excitotoxic insult and support its potential use as a treatment for central nervous system disorders that may be a consequence of excitotoxic processes, such as Huntington's disease.
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PMID:Glial cell line-derived neurotrophic factor attenuates the excitotoxin-induced behavioral and neurochemical deficits in a rodent model of Huntington's disease. 933 Mar 71


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