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)

Aluminum-induced neurofibrillary degeneration in rabbits is known to affect particular populations of neurons. The neurotransmitter alterations which accompany aluminum neurofibrillary degeneration were examined in order to assess how closely they mimic those of Alzheimer's disease. There was a significant reduction in choline acetyltransferase activity in entorhinal cortex and hippocampus as well as significant reductions in cortical concentrations of serotonin and norepinephrine in the aluminum-treated rabbits. Significant reductions in glutamate, aspartate and taurine were found in frontoparietal and posterior parietal cortex. Concentrations of GABA were unchanged in cerebral cortex. Both substance P and cholecystokinin immunoreactivity were significantly reduced in entorhinal cortex but there were no significant changes in somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. The five neuropeptides were unaffected in striatum, thalamus, cerebellum and brainstem. Neurochemical changes were found in the regions with the most neurofibrillary degeneration while regions with little or no neurofibrillary degeneration were unaffected. The reductions in choline acetyltransferase activity, serotinin and noradrenaline suggest that some neuronal populations preferentially affected in Alzheimer's disease are also affected by aluminum-induced neurofibrillary degeneration; however, the cortical somatostatin deficit which is a feature of Alzheimer's disease is not replicated in the aluminum model.
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PMID:Neurochemical characteristics of aluminum-induced neurofibrillary degeneration in rabbits. 256 53

Immunohistochemical techniques were used to survey the distribution of several conventional transmitters, receptors, and neuropeptides in the pigeon nucleus of the basal optic root (nBOR), a component of the accessory optic system. Amongst the conventional neurotransmitters/modulators, the most intense labeling of fibers/terminals within the nBOR was obtained with antisera directed against glutamic acid decarboxylase (GAD) and serotonin (5-HT). Moderately dense fiber plexuses were seen to label with antibodies directed against tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). GAD-like immunoreactivity (GAD-LI) was found in many small and medium-sized perikarya within the nBOR. Some of the medium-sized cells were occasionally positive for ChAT-LI. Cell body and dendritic staining was also commonly seen with the two tested antisera against receptors-anti-GABA-A receptor and anti-nicotinic acetylcholine receptor. The antisera directed against various neuropeptides produced only fiber labeling within the nBOR. The densest fiber plexus staining was observed with antiserum against neuropeptide Y (NPY-LI), while intermediate fiber densities were seen for substance P (SP-LI) and cholecystokinin (CCK-LI). A few varicose fibers were labeled with antisera against neurotensin (NT), leucine-enkephalin (L-ENK), and the vasoactive intestinal polypeptide (VIP). Unilateral enucleation produced an almost complete elimination of TH-LI in the contralateral nBOR. SP-LI and CCK-LI were also decreased after enucleation. No apparent changes were seen for all other substances. These results indicate that a wide variety of chemically-specific systems arborize within the nBOR. Three of the immunohistochemically defined fiber systems (TH-LI, SP-LI, and CCK-LI fibers) were reduced after removal of the retina, which may indicate the presence of these substances in retinal ganglion cells. In contrast, the fibers exhibiting ChAT-LI, GAD-LI, 5-HT-LI, NPY-LI, NT-LI, L-ENK-LI, and VIP-LI appear to be of nonretinal origin. Two different populations of nBOR neurons exhibited GAD-LI and ChAT-LI. However, these two populations together constituted only about 20% of the nBOR neurons.
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PMID:Neurotransmitters, receptors, and neuropeptides in the accessory optic system: an immunohistochemical survey in the pigeon (Columba livia). 257 70

The first part of this chapter demonstrates that the C1 adrenergic neurons have high mitochondrial content and a close proximity to capillaries and glia suggestive of a high metabolic activity and a possible chemosensory function. Adrenergic terminals arising primarily from these neurons (1) can influence sympathetic nerve discharge through direct contacts on sympathetic preganglionic neurons in the IML of the spinal cord; and (2) are one of the more prevalent synaptic inputs to the principally noradrenergic neurons in the locus coeruleus. In both the IML and locus coeruleus, adrenergic terminals may be either excitatory (asymmetric synapses) or inhibitory (symmetric synapses) depending on their distribution on the post-synaptic target. The second part of this chapter shows that C1 adrenergic neurons in the RVL are modulated by synaptic associations with a variety of transmitter systems (see schematic Fig. 8). Specifically, C1 adrenergic neurons receive (1) major inhibitory input (symmetric synapses) from GABA-ergic and opioid terminals as well as from unidentified (unlabelled) transmitter-containing terminals; (2) major excitatory input (asymmetric synapses) from terminals containing substance P as well as other unidentified terminals and (3) minor inputs from cholinergic, adrenergic and noradrenergic pathways. Moreover, cholinergic terminals in the RVL form symmetric synapses mainly on unidentified transmitter-containing neurons rather than the C1 neurons suggesting that the reported cardiovascular effects of cholinergic agents in the RVL are most likely mediated via inhibitory interneurons. Within the RVL, adrenergic and noradrenergic terminals innervate cholinergic and opioid neurons. Thus, these results not only provide direct evidence that a number of transmitters modulate the activity of C1 adrenergic neurons, but also suggest new directions for studies of functional interactions involving catecholaminergic regulation of other transmitter-containing neurons within the RVL.
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PMID:Adrenergic neurons in the rostral ventrolateral medulla: ultrastructure and synaptic relations with other transmitter-identified neurons. 269 22

In Parkinson's disease the progressive loss of nigrostriatal dopamine neurons leads to striatal dopamine deficiency and correlates with the severity of parkinsonian disability. The findings concerning dopamine receptors both in vitro and in vivo are not consistent, possibly reflecting differences in patient populations, but the presynaptic defect in dopaminergic neurotransmission is greater than that seen in postsynaptic receptor binding studies. The cholinergic neurons in the extrapyramidal nuclei are relatively well preserved, but subcortico-cortical and -hippocampal cholinergic neurons degenerate in relation to the degree of dementia. The decreased GABA receptor binding in the parkinsonian substantia nigra possibly reflects the loss of nigral dopamine neurons, since nigral GABA receptors are located on these neurons. Of the various neuropeptides, the concentration of met- and leu-enkephalin seems to be reduced in the striatum. In the substantia nigra the concentration of substance P decreases, together with the met-enkephalin and cholecystokinin levels. The concentration of somatostatin decreases in the frontal cortex and hippocampus of demented patients. With the exception of the association between cortical somatostatin deficiency and intellectual deterioration, the role of the neuropeptides in the pathophysiology and clinical features of Parkinson's disease are not yet fully understood.
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PMID:Chemical neurotransmission in the parkinsonian brain. 282 31

The study of neurotransmitter receptors aids in the understanding of the normal anatomy, pharmacology, therapeutics and pathophysiology of disease processes involving the basal ganglia. Receptors may be studied in vitro by homogenate binding experiments, enzyme analysis or quantitative autoradiography and in vivo with positron emission tomography. In the substantia nigra (SN), receptors have been identified for somatostatin, neurotensin, substance P, glycine, benzodiazepine and GABA, opiates, dopamine, angiotensin converting enzyme (ACE) and serotonin. The striatum has receptors for dopamine, GABA and benzodiazepines, acetylcholine, opiates, substance P, glutamate and cholecystokinin. GABA and benzodiazepine receptors are also located in the globus pallidus. In Parkinson's disease, striatal dopamine D-2 receptors are elevated in patients that have not received L-DOPA therapy. This supersensitivity is reversed with agonist therapy. Muscarinic binding to cholinergic receptors seems to correlate with dopamine receptors. Delta opiate receptors are increased in the caudate and mu binding is reduced in the striatum. In the SN of patients with Parkinson's disease, there is reduced binding of somatostatin, neurotensin, mu and kappa opiates, benzodiazepine and GABA and glycine. In Huntington's disease, there is reduced binding of GABA and benzodiazepines, dopamine, acetylcholine, glutamate and CCK. There is increased binding of GABA in both the SN and globus pallidus. Glycine binding is increased in the substantia nigra and ACE is reduced.
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PMID:Receptors in the basal ganglia. 282 9

The influence of alpha-chymotrypsin and diazepam on the phasic (mainly direct) and tonic (indirect, probably substance P-mediated) components of intestinal cholinergic contractions, induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (3-APS), was investigated in the guinea-pig ileum. alpha-Chymotrypsin, at a concentration (20 U/ml) not affecting submaximal Ach (0.1 microM) contractions, preferentially depressed the tonic component of the 3-APS (30 microM)-induced response. A brief exposure (10 or 60 sec) to diazepam (0.1 microM) potentiated both the phasic and the tonic contractions evoked by low (10, 30 microM) 3-APS concentrations. This potentiation was prevented by bicuculline (30 microM), hyoscine (1 microM) and flumazenil (1, 3 microM). These results provide further support for an involvement of a peptide neurotransmitter on GABA-A receptor-mediated cholinergic response in the ileum. The modulation of this response by diazepam is probably exerted through recognition sites resembling the "central type" benzodiazepine receptors.
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PMID:Cholinergic contractions induced by GABA-A receptor activation in the guinea-pig ileum are inhibited by alpha-chymotrypsin and potentiated by diazepam. 285 13

The striatum receives massive dopaminergic projections from neurons in the ventral tegmental area, the substantia nigra and the retro-rubral cell group. Dopaminergic neurons in the arcuate nucleus and periventricular hypothalamic nuclei project to the median eminence and the neuro-intermediate lobe of the pituitary gland. The anterior lobe of the pituitary gland is not innervated by dopaminergic neurons, but receives dopamine via a vascular route from the median eminence. Two categories of dopamine receptors (D-1 and D-2) can be identified on the basis of the ability of various drugs to discriminate between these two entities. Dopamine stimulates both D-1 and D-2 receptors. The affinity of dopamine for the D-2 receptor is approximately 1000 times higher than for the D-1 receptor. Dopamine is involved in synaptic as well as non-synaptic communication. Examples of non-synaptic communication via D-2 receptors are the dopamine induced inhibition of prolactin release from the anterior pituitary gland and most likely the D-2 receptor mediated inhibition of the release of acetylcholine in the striatum. Examples of synaptic communication have been found in the striatum where (with ultrastructural techniques) synaptic contacts between dopaminergic nerve terminals and elements from cells containing GABA, substance P or enkephalin have been demonstrated. It is tempting to speculate that synaptic and non-synaptic communication occurs via D-1 and D-2 receptors respectively.
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PMID:Localization and pharmacology of some dopamine receptor complexes in the striatum and the pituitary gland: synaptic and son-synaptic communication. 285 85

Neurotransmitter abnormalities in the basal ganglia of individual "choreic" patients (9 cases of Huntington's disease-HD and 3 cases of dentatorubropallidoluysian atrophy-DRPLA) and 14 normal controls were investigated. Choline acetyltransferase activity in the striatum was decreased in approximately half the "choreic" patients. GABA concentration in the substantia nigra or in the globus pallidus was decreased in all "choreic" cases except one case of DRPLA. Substance P concentration was also reduced in the same nuclei as GABA except in one case of HD. These findings imply: cholinergic, GABAergic or substance P-related markers found in the basal ganglia of HD are not disease-specific but also found in the other "choreic" disorder, i.e. DRPLA; most prominent biochemical changes in HD would be a decrease of GABA in the basal ganglia. Correlation analysis of the markers in the basal ganglia and the striatal neurone densities of "choreic" patients (5 cases of HD and 3 cases of DRPLA) and 7 normal controls yielded positive correlation between GABA concentration in the substantia nigra and the globus pallidus, and the neuronal cell density in "small" cells in the striatum of normal control and HD. Positive correlation between substance P concentration and the striatal neurone density was only found in the substantia nigra. Choline acetyltransferase activity in the striatum was found to be positively correlated with the density of "large" cells in the striatum rather than that of "small" cells. In DRPLA there was no direct correlation between the values of the markers in the basal ganglia and the striatal neurone density. The decrease of transmitter markers without striatal cell loss in this particular choreic disorder could be regarded as a sequence of "biochemical degeneration" of striatal neurones. Based on these findings, the underlying mechanisms of choreic involuntary movements were briefly discussed.
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PMID:Studies on neurotransmitter markers and striatal neuronal cell density in Huntington's disease and dentatorubropallidoluysian atrophy. 286 38

The effects of neurotransmitters or drugs on the release of endogenous dopamine (DA) and extracellular levels of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were examined in vivo by intracerebral dialysis. A dialysis tube was implanted stereotaxically through bilateral caudate nuclei of rats and perfused with the Ringer solution. Amounts of DA, DOPAC and HVA in the perfusates were measured by high performance liquid chromatography (HPLC) with electrochemical detection. The basal level of DA was 2.76 +/- 0.64 pg/min, whereas the levels of DOPAC and HVA were 218.7 +/- 20.7 and 142.4 +/- 10.6 pg/min, respectively. Apomorphine (4 mg/kg, i.v.) reduced the efflux of DA and its metabolites. Haloperidol (0.4 mg/kg, i.v.) did not change DA release and produced only a minor increase of its metabolites. This increase of metabolites was inhibited by pargyline. Met-enkephalin (10(-4) M), substance P (10(-4) M) and acetylcholine chloride (10(-4) M) added to the perfusing medium increased the release of DA. Met-enkephalin also increased the release of DOPAC. gamma-Amino-n-butyric acid (GABA, 10(-4) M) reduced the release of DOPAC and HVA when added to the perfusing medium. Thyrotropin releasing hormone (TRH, 5 mg/kg, i.v.) increased the release of HVA. These findings indicated that different mechanisms mediated effects of neurotransmitters or drugs on the release and metabolism of DA in the rat striatum.
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PMID:Effects of neurotransmitters or drugs on the in vivo release of dopamine and its metabolites. 287 Feb 4

While the dentate gyrus is clearly the simplest of the cortical fields that constitute the hippocampal formation, it nonetheless occupies a pivotal position in the flow of information through this region. Though it has been the subject of anatomical study for over a century and its major connections have been known for almost as long, the use of newly developed histochemical and immunohistochemical techniques have demonstrated many new facets of its intrinsic connectivity and afferent innervation. These techniques have established that it is innervated by cholinergic, noradrenergic, serotonergic and dopaminergic fibers. More recent studies have shown that fibers and cell bodies of the dentate gyrus are immunoreactive for variety of neuroactive substances including the excitatory amino acids glutamate and aspartate, the inhibitory transmitter GABA, as well as peptides of many types including the opioid peptides, enkephalin and dynorphin, several forms of somatostatin, neuropeptide Y, cholycystokinin, vasoactive intestinal peptide and substance P. In this review, we will briefly summarize the distribution of each of these putative transmitter systems within the dentate gyrus. The perspective emerges that the plethora of newly identified and chemically specific fiber systems enriches the classical understanding of the organization of this relatively simple cortical structure. Since there is thus far no evidence for the exclusion from the dentate gyrus of any class of transmitter bearing fiber or neuron found in the neocortex, it can be viewed as a relatively simple model system for studying the interactions of specific transmitter systems in a laminated, cortical structure.
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PMID:Transmitter systems in the primate dentate gyrus. 287 75


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