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)

In this study we investigated the effects of possible modulatory transmitters on acoustically responsive neurons of the caudal pontine reticular nucleus (PnC). From previous work in our laboratory it has been suggested that the acoustically responsive giant neurons of this nucleus are the sensorimotor interface mediating the acoustic startle response. Furthermore they are the site of some of the modulatory influence impinging on this response. Besides a possibly glutamatergic excitation from the amygdala a cholinergic input from the midbrain has been described which may use substance P as cotransmitter. Therefore we used electrophysiological and histochemical methods to study this possible modulatory influence in the caudal pontine reticular nucleus. In the first part of this study we recorded extracellularly from single units in the PnC in vivo and studied the effects of iontophoretically applied transmitters. Substance P elicited a long lasting excitation. This excitatory effect of SP was potentiated by acetyl-beta-methylcholine (AMCh, an acetylcholine agonist), whereas single application of AMCh showed no uniform response. Glutamate elicited a potent brief excitation, while application of GABA showed a potent brief inhibition of PnC neurons. In the second part of this study we employed immunoperoxidase staining for substance P, which revealed a fairly dense network of substance P-immunoreactive (SP-ir) fibers in the lateral and ventral aspects of the PnC. Combining retrograde tracing and immunocytochemistry for substance P, we demonstrated that the SP-ir axons in the PnC originate mainly in the laterodorsal tegmental nucleus. We therefore conclude that activation of the laterodorsal tegmental nucleus may facilitate the acoustic startle response by a long lasting excitation of neurons in the caudal pontine reticular nucleus.
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PMID:Substance P and other putative transmitters modulate the activity of reticular pontine neurons: an electrophysiological and immunohistochemical study. 751 29

The segmental and laminar origin of propriospinal antinociceptive systems in the cat spinal cord and the modes to activate them are characterized. The experiments were performed on pentobarbital-anesthetized cats with a high cervical spinalization. Recordings were made from single lumbar spinal dorsal horn neurons responding to noxious radiant skin heating and to innocuous mechanical skin stimuli. The segmental and laminar origin of heterosegmental, propriospinal neurons modulating background activity and nociceptive responses were identified and the conditions to activate them were characterized. Conditioning noxious front paw stimulation and superfusion of the cervical enlargement with L-glutamate, but not with substance P, reduced noxious heat-evoked responses of about 50% of all lumbar neurons tested. Glutamate superfusions of the lower thoracic or upper sacral spinal cord enhanced background activity and reduced nociceptive responses of most lumbar spinal dorsal horn neurons. Superfusions with substance P or somatostatin were ineffective. Glutamate microinjections into the superficial layers of the thoracic, upper lumbar or sacral dorsal horn ipsi- or contralateral to the recording sites or into lamina VIII of the ipsilateral thoracic or upper lumbar cord reduced noxious heat-evoked responses with or without changes in the level of background activity. It is concluded that propriospinal neurons originating from circumscribed areas of the cervical, thoracic, lumbar or sacral spinal cord independently modulate background activity and noxious heat-evoked responses of multireceptive lumbar spinal dorsal horn neurons. The incidence and efficacy of propriospinal antinociceptive stimulation sites was found to be as high as for the classical region of endogenous antinociception, the midbrain periaqueductal gray.
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PMID:Characteristics of propriospinal modulation of nociceptive lumbar spinal dorsal horn neurons in the cat. 768 6

The biological function of the soluble form of the amyloid beta-protein (ABP) was examined by assaying its interaction with neuronal receptors expressed in Xenopus oocytes. ABP weakly activated tachykinin receptors, but in the presence of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4- propionate-type glutamate receptors ABP-induced responses were greatly enhanced. Glutamate and ABP together also induced accumulation of inositol trisphosphate and increases in intracellular Ca2+. These observations suggest that in the presence of glutamate, ABP can activate tachykinin receptors and phosphatidylinositol turnover. ABP may therefore act as a neuromodulatory peptide.
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PMID:Amyloid beta-protein activates tachykinin receptors and inositol trisphosphate accumulation by synergy with glutamate. 768 20

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

Glutamate (Glu) and the tachykinin substance P (SP) have been proposed as neurotransmitters or neuromodulators of the retinal projection to the brain. In the present study, we demonstrate that tachykinin-like (TK) immunoreactivity (IR) accumulates in rat retinal axons following electrical lesions to the optic tract, indicating that SP is conveyed in the optic nerve to its central targets. In addition, we show that eye enucleation causes a dramatic decrease in TK-IR fibers in the pretectal olivary nucleus (PON), but not in other retinorecipient nuclei of the thalamus and the midbrain, and that Fluorogold injected into the pretectum is retrogradely transported to the somata of TK-IR retinal ganglion cells (RGCs), indicating an important projection of TK-IR RGCs to the PON. We also show that most rat RGCs are labeled with antibodies against phosphate-activated glutaminase, an enzyme considered to generate the transmitter pool of glutamate. Unlike TK-IR fibers, phosphate-activated glutaminase-IR structures disappear in most retinorecipient nuclei following eye enucleation. The present results give neuroanatomical support to the idea that glutamate is a neurotransmitter in the retinal projection and suggest an important role for TK-IR RGCs in the relay of visual information to the PON.
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PMID:Projections of tachykinin- and glutaminase-containing rat retinal ganglion cells. 795 61

Glutamate is a major neurotransmitter of fine afferent fibers to the spinal cord. Neuropeptides are also released by the same fibers. We explored, by quantitative immunocytochemistry, the effects of two experimental manipulations of peripheral nerves on the levels of these two classes of mediators. Glutamate levels in the superficial dorsal horn of rats increased after chronic loose ligature of the sciatic nerve, a model for hyperpathic peripheral neuropathy. A similar increase was observed acutely, after stimulation of C fibers, but not A fibers, in the sciatic nerve. In contrast, immunostaining for substance P and calcitonin gene-related peptide decreased in the same region with both manipulations. The decrease in immunocytochemical levels of peptides is in agreement with previous observations and can result from activity-related depletion. We propose that the increase in glutamate levels reflects differences in the regulation and kinetics of amino acid versus peptide neuromediators.
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PMID:Glutamate immunocytochemistry in the dorsal horn after injury or stimulation of the sciatic nerve of rats. 809 61

Immunocytochemical studies using antibodies raised against a number of probable synaptic transmitters of the mesodiencephalic area, and fibre-tracing studies using wheat germ agglutinin-horseradish peroxidase (WGA-HRP), have been performed in adult cats. Glutamate and aspartate immunoreactivity produced a strong labelling of many cell bodies and terminals in the nucleus of Darkschewitsch (ND). gamma-Aminobutyrate (GABA) immunoreactivity in the ND appeared as a moderate label in some small neurones, and as a strong label in a few glial-like cells, in addition to being present in high levels to produce strong labelling in many GABA-immunopositive terminals that possessed pleomorphic vesicles. Some choline acetyltransferase-positive terminals and dendrites and a few substance P-positive fine fibres possessing varicosities also were observed in the ND. Following WGA-HRP injection in the ND, dense terminal labelling was seen ipsilaterally in the rostral half of the medial accessory olive, suggesting that there may be a certain degree of mediolateral and dorsoventral topographic correspondance within the ND-olive projection. In the same cases, many cell bodies containing HRP reaction product also were found 1) ipsilaterally in the motor cortex, anterior pretectal nucleus, and a restricted area of the caudal part of the substantia nigra pars reticulata; 2) contralaterally in the anterior and posterior interposed cerebellar nuclei as well as in a portion of the lateral cerebellar nucleus; and 3) bilaterally in the zona incerta, the posterior pretectal nucleus, the pedunculopontine tegmental nuclei, the spinal trigeminal nucleus, the dorsal column nuclei, and the spinal cord. Details of the interrelationships and functional considerations amongst the ND, adjacent nuclei, and longitudinal zones of the cerebellum are discussed.
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PMID:Patterns of transmitter labelling and connectivity of the cat's nucleus of Darkschewitsch: a wheat germ agglutinin-horseradish peroxidase and immunocytochemical study at light and electron microscopical levels. 857 14

In a previous study, we have found acetylcholine and/or L-DOPA in 10 colonial clones from one cell line of Drosophila larval central nervous system (CNS). In this study, to characterize clonal neuronal phenotypes further, we have examined three neuropeptides and 19 amino acids using HPLC system. Substance P and proctolin were found in seven and eight out of ten clones, respectively. On the other hand, somatostatin was expressed in all ten clones. GABA and taurine were not detected in any clones. Glutamate, which is an excitatory transmitter in Drosophila, was found in all the clones, although its content was different seven times among them. Glycine, which is not known as a transmitter in Drosophila, was found to be unevenly expressed among them. Therefore, the conspicuous expression of peptides or amino acids in some clones suggests that the substances have a special role in Drosophila CNS.
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PMID:Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system, II: Neuropeptides and amino acids. 858 6

A cortical infarct of 2 mm diameter was obtained in the parietal cortex after a craniotomy, disruption of the dura mater and topical application of 3 M KCl. It has been shown previously that the presence of a small cortical infarct induces an increase in immediate early gene messenger RNA expression followed by an increase in neuropeptide and glutamic acid decarboxylase messenger RNA expression. Glutamate, acting at N-methyl-D-aspartate receptors, is held responsible for these changes, since they are blocked by pretreatment with dizocilpine. In the present study, we have analysed the consequences of the dramatic changes in messenger RNA expression on the level of immediate early gene products c-fos and zif 268, and on that of neuropeptides by using immunohistochemistry. After just 1 h, an increase in c-fos- and zif 268-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct, and is no longer detected after 6 h. An increase in cholecystokinin octapeptide-, substance P-, neuropeptide Y- and somatostatin-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after 30 days. To investigate if these dramatic increases in neuropeptide immunoreactivities may have functional consequences, we studied the level of cholecystokinin receptors by autoradiographic binding using [125I]cholecystokinin-8S and in situ hybridization for the detection of cholecystokinin-b receptor messenger RNA. A decrease in cholecystokinin binding sites and cholecystokinin-b receptor messenger RNA is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after nine days. This study shows that a topical stimulation has diffuse effects, reaching regions far from the site of the lesion, and some of them are still strongly present after nine days. The increase in neuropeptide messenger RNAs is followed by an increase in the protein products of these genes, which may modify the neurotransmission. As a corollary to this, a decrease in cholecystokinin binding sites occurs. This may have further consequences on signal transduction pathways. This decrease in cholecystokinin binding sites is associated with a decrease in the cholecystokinin-b receptor messenger RNA, and this is the first example of a decrease in messenger RNA levels in this experimental model.
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PMID:Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction. 859 53

This review summarises our current understanding of the neurotransmitters involved in the generation, transmission and modulation of respiratory rhythm. The principal neurotransmitters involved in generating and transmitting respiratory rhythm include glutamate, GABA, and glycine. Glutamate acts primarily at non-NMDA receptors within the networks to generate respiratory rhythm in neonatal in vitro preparations, but it may also engage NMDA receptors in mature intact animals. Glutamate may likewise act as presynaptic AP-4 metabotropic receptors to fine tune its own release in the transmission of respiratory rhythm to the phrenic motoneurones. The role of other metabotropic receptors in rhythmogenesis is not known. GABA (primarily by acting at GABAA receptors), as well as glycine, transmit phasic waves of inhibition within the primary respiratory network. Neuroactive agents synthesized outside the primary network may shape the final expression of the basic rhythm. The most studied inputs originate in the pons and from the slowly adapting pulmonary stretch receptors (SAR). Both of these inputs contribute to the transition from inspiration to expiration. Pontine mechanisms rely on excitatory amino acid activation of NMDA receptors, while SAR pathways utilize non-NMDA receptors. Serotonin has also been implicated in regulating respiratory rhythm, possibly via serotonergic projections originating in the raphe nuclei. The amine has diverse effects on respiratory neuronal activity; the most consistent effect appears to be an augmentation of phrenic motoneuronal at the level of the spinal cord. Substance P regulates respiratory activity by acting in the CNS and on peripheral sensory receptors. Centrally, substance P largely augments respiration, by increasing respiratory rhythm in neonatal in vitro preparations and also by increasing tidal volume in the intact animal. Substance P is also released by carotid chemoreceptor afferents during hypoxia. Opioids are well known to decrease respiration; the central mechanism involves the suppression of baseline inspiratory neuronal activity and possibly the blunting of glutamate-evoked increases in inspiration drive.
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PMID:Neurotransmitters in the CNS control of breathing. 860 95


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