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)

In order to better understand the neuroleptic-like effects of neurotensin in vivo, the effects of neurotensin in vitro on dopamine D2 and D1 agonist and antagonist binding sites were characterized in membranes from the neostriatum and the subcortical limbic area. Neurotensin increased the KD but not the Bmax value of S(-)[N-propyl-3H(N)]propylnorapomorphine [( 3H]NPA) binding sites with a maximal increase of 20-40% at 3-10 nM of neurotensin in both areas. The KD increase was preferentially due to an increase in the dissociation rate. The maximal reduction of [3H]NPA binding (35%) was obtained within 5 min from the addition of neurotensin. Neurotensin increased the KH of dopamine vs [3H]raclopride binding and, in the presence of GTP, also KL. Neurotensin did not affect the percentage of binding sites in the high vs low affinity states or the binding characteristics of [3H]spiperone, [3H]SKF 38393, and [3H]SCH 23390. Serotonin (10 nM), neuropeptide Y (10 nM), Substance P (10 nM), dynorphin A (10 nM), morphine (10 nM), nicotine (100 nM), gamma-amino-n-butyric acid (1 microM), or N-methyl-D-aspartate (1 microM) did not affect [3H]NPA binding. These results indicate that neurotensin in vitro selectively reduces D2 agonist affinity by an enhancement of the dissociation rate. This antagonistic intramembrane interaction may underlie the neuroleptic-like effects of neurotensin at low concentrations in vivo on D2 agonist binding, dopamine release, and on D2-mediated behaviours.
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PMID:Biochemical characterization of the intramembrane interaction between neurotensin and dopamine D2 receptors in the rat brain. 183 40

Excitatory amino acid (EAA)-induced cell death in the striatum is dependent upon intact glutamatergic afferents arising from the cerebral cortex. Through a mechanism possibly related to inhibition of glutamate release, adenosine receptor agonists attenuate EAA induced toxicity in the rat striatum. In the present study, we examined whether 2-chloroadenosine (2CLA), a stable adenosine analog, protects against toxicity induced by kainate (KA), quisqualate (QUIS), N-methyl-D-aspartate (NMDA), and ibotenate (IBO). In vivo intrastriatal injections of 2CLA (50 nmol) with each EAA tested provided a partial but significant protective effect versus injection of the EAA alone, as measured by striatal concentrations of gamma-aminobutyric acid (GABA) and substance P-like immunoreactivity (SP-LI). These results show that 2CLA attenuates both NMDA- and non-NMDA-mediated neuronal cell death.
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PMID:2-Chloroadenosine attenuates NMDA, kainate, and quisqualate toxicity. 192 33

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

In the present study we investigated the relative vulnerability of neuronal subsets in the striatum to ischemia that was induced by bilateral transient ligation of the common carotid arteries in gerbils. After 4 days of survival, brains were evaluated using histochemical methods (NADPH-diaphorase and silver degeneration procedures) and neurochemical methods with radioimmunoassays for somatostatin-, neuropeptide Y-, and substance P-like immunoreactivity and measurements of amino acids using high-pressure liquid chromatography with electrochemical detection. NADPH-diaphorase-positive neurons were strikingly preserved in the ischemic dorsolateral portion of the striatum, in which there was severe neuronal loss. There was no significant depletion of NADPH-diaphorase-positive neurons in the striatum or cerebral cortex. Concentrations of neuropeptide Y-like and somatostatin-like immunoreactivity were unchanged despite a significant 25% depletion of substance P-like immunoreactivity and gamma-aminobutyric acid. Ischemic brain damage may be mediated by a neurotoxic effect of glutamate acting at the N-methyl-D-aspartate (NMDA) receptor. Previous studies of NMDA excitotoxin lesions in rat striatum have shown a sparing of neurons containing NADPH-diaphorase, somatostatin, and neuropeptide Y. The similar sparing of these neurons following ischemic lesions in gerbil striatum provides further evidence that NMDA receptor activation may play a role in ischemic injury.
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PMID:Selective sparing of NADPH-diaphorase-somatostatin-neuropeptide Y neurons in ischemic gerbil striatum. 197 76

The opioid peptide dynorphin A (1-17) is the third transmitter identified in the striatonigral projection, the other two being gamma-aminobutyric acid (GABA) and substance P. The ultrastructural features of the dynorphinergic terminals in substantia nigra/pars reticulata were studied using pre-embedding immunocytochemistry with the classical peroxidase-antiperoxidase-diaminobenzidine-method; these features were compared with GABAergic boutons visualized with an immunogold method. Two distinct types of dynorphin-A-immunoreactive boutons could be identified: (1) type A (81%) possessing characteristics similar to the GABAergic nerve endings in this region, i.e., large pleomorphic vesicles and symmetric synaptic contacts; (2) type B (19%) displaying asymmetric synaptic zones and small, mostly round vesicles. These results are in agreement with physiological studies suggesting a dual action of dynorphin A in substantia nigra.
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PMID:Two different types of dynorphin-A-immunoreactive terminals in rat substantia nigra. 197 80

The effects of injections of gamma-aminobutyric acid (GABA) and dynorphin A into the substantia nigra, pars reticulata on the levels of extracellular dopamine (DA) and GABA in the ipsilateral striatum of halothane-anaesthetized rats were studied using microdialysis. The effects of intranigral injections of substance P and neurokinin A were also studied. Intranigral GABA (300 nmol) or dynorphin A (0.5 nmol) injections produced a simultaneous decrease in DA and increase in GABA levels, while intranigral substance P (0.07 nmol) or neurokinin A (0.09 nmol) injections produced an increase in DA but had no effect on GABA levels. DA agonists, apomorphine (D1/D2), SKF 38393 (D1) and pergolide (D2) were applied locally by perfusing them through the microdialysis probe, each at a concentration of 10(-5) M. All 3 agonists decreased the levels of DA in the striatum. However, while apomorphine and SKF 38393 increased, pergolide decreased the levels of GABA in the striatum. The increase in striatal GABA produced by intranigral injections of GABA (300 nmol) was reversed by local perfusion with pergolide (10(-5) M), but was not reversed by local perfusion with SKF 38393 (10(-5) M). These findings suggest that D1 and D2 receptors differentially regulate striatal GABA release, and are stimulatory and inhibitory, respectively. Furthermore, it is suggested that nigrostriatal DA functions as an inhibitory modulator of striatal GABA neurons, acting via D2 receptors.
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PMID:The effects of intranigral GABA and dynorphin A injections on striatal dopamine and GABA release: evidence that dopamine provides inhibitory regulation of striatal GABA neurons via D2 receptors. 197 63

The avian wulst, a laminated "bulge" in the dorsal telencephalon, contains several distinct regions. The posterolateral portion (visual wulst) has been proposed to be an avian equivalent of the mammalian striate cortex. The present study examines specific neurotransmitters and neuropeptides within the visual wulst by immunohistochemical techniques. Antisera and monoclonal antibodies against choline acetyltransferase (ChAT), nicotinic acetylcholine receptor (nAChR), tyrosine hydroxylase (TH), serotonin (5-HT), glutamic acid decarboxylase (GAD), gamma-aminobutyric acid A receptor (GABAAR), cholecystokinin (CCK), substance P (SP), leucine-enkephalin (L-ENK), neurotensin (NT), neuropeptide Y (NPY), somatostatin (SRIF), corticotropin-releasing factor (CRF), and vasoactive intestinal polypeptide (VIP) were used. Somata and neuropil displaying specific immunoreactivity were generally distributed in accordance with the laminar cytoarchitectonic organization of the wulst. The superficial layer of the wulst, the hyperstriatum accessorium, contained the highest densities of TH-, 5-HT-, SP-, NPY-, SRIF-, CRF-, and VIP-positive neuropil in the wulst, whereas the highest density of CCK- and NT-staining was found in the deepest layer of the wulst, the hyperstriatum dorsale. In addition to the traditionally defined four laminae of the wulst, the immunoreactive staining revealed several subregions within each lamina. The most dorsolateral portion of the wulst contained the highest densities of ChAT- and L-ENK-stained fibers in the wulst, as well as moderately dense staining of neuropil for 5-HT-, TH-, SP-, and CCK-like immunoreactivity. The nAChR-immunoreactivity was faint and distributed rather uniformly throughout the wulst. The results suggest that the wulst consists of multiple regional variations within layers comparable to laminar variations found within different cytoarchitectonic areas of the mammalian neocortex.
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PMID:Immunohistochemical analysis of the visual wulst of the pigeon (Columba livia). 197 83

The active immunization of rabbits and white rats to antidepressant sydnophen results in the formation of antibodies binding norepinephrine, dophamine, serotonine as well peptide regulatory compounds: substance P, pynorphine, vasopressin and beta-endorphin. The immunization against endogenic antidepressant thyroliberin induces the formation of antibodies to the same biogenic amines and to the gamma-aminobutyric acid, oxytocin and leu encephalin. The data obtained are discussed in connection with some physiological and biochemical changes found earlier during immunization to antidepressants.
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PMID:[Active immunization to exogenous and endogenous antidepressants. The formation of antibodies to biogenic amines and peptide regulators]. 205 18

The distribution and fine structure of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) cells and fibers in the vestibular nuclei of the rat were investigated by light and electron microscopic immunocytochemistry. In addition to the previous report that CGRP-LI cells were found in the lateral vestibular nucleus, the present study clarified that they are found also in the inferior vestibular nucleus, medial vestibular nucleus and nucleus X. The lateral vestibular nucleus contains a high density of CGRP-LI cells. They are medium in size and multipolar in shape. CGRP-LI cells in the inferior vestibular nucleus are small to medium in size and triangular or pea shaped. CGRP-LI cells in the medial vestibular nucleus and nucleus X are both few in number and small in size. Possible colocalization of CGRP with acetylcholine, gamma-aminobutyric acid or substance P in the single neuron of the vestibular nuclei might be suggested. CGRP-LI fibers are more extensively distributed in various areas throughout the vestibular nuclei, though previous studies reported that they were found in the lateral vestibular nucleus and inferior vestibular nucleus. A number of CGRP-LI fibers are clearly observed in the inferior vestibular nucleus. Under electron microscopic analysis, CGRP-LI endoproducts are diffusely localized throughout the cytoplasm and some of CGRP-LI dendrites are identified to receive synaptic inputs form non-immunoreactive axon terminals with small spherical vesicles. It seems likely that CGRP is participated both in the intrinsic neurons in the vestibular nuclei or in the reciprocal innervations between the vestibular nuclei and the reticular formation or the cerebellum.
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PMID:[Localization of calcitonin gene-related peptide-like immunoreactivities in the vestibular nuclei of the rat by light and electron microscopic studies]. 228 Mar 11

The role of spinal cord substance P (SP) in regulating sympathetic outflow to the cardiovascular system was assessed with the stable active analog [pGlu5,MePhE8,MeGly9]-SP(5-11) (DiME-SP). The interaction of DiME-SP with spinal cord SP receptors was evaluated initially in binding studies. Saturable, high-affinity binding of [125I]Bolton-Hunter-SP to rat spinal cord membranes was dose-dependently inhibited by DiME-SP (IC50 = 1.5 microM). Intrathecal (i.t.) injections of DiME-SP (1.0-33 nmol) in anesthetized rats produced dose-dependent increases in blood pressure and heart rate that were accompanied by increases in plasma epinephrine and norepinephrine. Intravenous injections of the ganglionic blocker pentolinium blocked the cardiovascular and plasma catecholamine responses to i.t. injections of DiME-SP. Bulbospinal sympathoexcitatory pathways originating in the ventral medulla and their mediation by SP were also assessed. As demonstrated previously, application of bicuculline, the gamma-aminobutyric acid receptor antagonist, to the ventral surface of the medulla produced sympathetic mediated increases in blood pressure and these effects were blocked by i.t. injection of the SP receptor antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP. In this study, we studied the specificity of the SP antagonist for SP receptors by attempting to alter the actions of the SP antagonist with a SP agonist. Administration of DiME-SP (33 nmol i.t.) blocked the effects of [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP (3.3 nmol i.t.). Specifically, the SP agonist countered the SP antagonist-mediated 1) hypotensive response and 2) inhibitory effect on bicuculline-induced sympathoexcitatory responses elicited from the ventral surface of the medulla. These data provide further evidence that SP transmits excitatory information to the cardiovascular system via spinal sympathetic pathways.
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PMID:Cardiovascular effects of spinal cord substance P: studies with a stable receptor agonist. 240 70


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