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)

Neuronal antigens can be demonstrated histologically by numerous direct and indirect immunocytochemical techniques in which a specific antibody is identified by a marker compound such as fluorescein isothiocyanate, ferritin, or horseradish peroxidase. One of the more sensitive methods for the light and electron microscopic localizations of antigens in sections of tissue is the peroxidase-antiperoxidase (PAP) technique. The experimental procedures and the results obtained using this technique for the localization of the catecholamine synthesizing enzyme, tyrosine hydroxylase, are described. The cellular and ultrastructural localization of the enzyme is demonstrated in perikarya, processes, and terminals of catecholaminergic neurons in rat brain. The immunocytochemical localization of tyrosine hydroxylase is compared to the localization of two peptides, substance P and [Met5]-enkephalin, in the A2 region of the medulla. These studies suggest that a synaptic interaction exists between the catecholaminergic neurons and neurons showing positive immunoreactivity for the peptides. The limitations of the PAP immunocytochemical technique are also discussed in relation to the immunocytochemical localization of tyrosine hydroxylase and other antigens.
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PMID:Immunocytochemical localization of neuronal antigens: tyrosine hydroxylase, substance P, [Met5]-enkephalin. 3 6

Neuronal compartments can be separated by differential spinning or by centrifugation on continuous or discontinuous density gradients. Application of these fractionation techniques to brain structures containing neurosecretory neurons shows that LHRH, somatostatin and a non dopamine prolactin inhibiting factor (PIF) are exclusively recovered from synaptosomal fractions. This indicates that biologically and/or immunologically reactive forms of these hormones are almost entirely concentrated in nerve-endings of neurosecretory neurons. In contrast, other neuropeptides - posterior pituitary hormone, but also TRH, a vasoactive intestinal peptide (VIP), substance P or endorphins - are also found in supernatant fractions. The existence of multiple molecular forms of neuropeptides is likely to explain these differences. Current theories postulate that they are synthetized on ribosomes as precursor forms. Their active structure is only achieved by enzymatic splitting of the pre- or the prohormone within nerve endings. This mode of synthesis is probably common to all neuropeptides, although it has only been well substantiated in a few cases, in particular for the hormones of the posterior pituitary. Thus, the lack of immunologically detectable LHRH or SRIF outside the synaptosomal fraction may reflect masking of the active immunological sites by inert peptide chains associated with prohormonal forms. Fractionation methods can also be applied to physiological or pharmacological experiments. In particular, they permit to characterize, on presynaptic membranes of neurosecretory neurons, specific receptors to neurotransmitters involved in the control of neurohormone secretion. Interaction of dopamine and acetylcholine with LHRH and CRF release are presented as examples of such applications.
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PMID:[Subcellular distribution of hypothalamic neurohormones and in vitro stimulation of their release]. 20 91

Neuronal hypertrophy occurs in a subpopulation of neurons in the infundibular nucleus of post-menopausal women. The hypertrophied neurons contain NKB, SP and estrogen receptor gene transcripts. Although associated with reproductive aging, post-menopausal neuronal hypertrophy is not a sign of central nervous system degeneration. Quite the opposite, because the hypertrophy is accompanied by marked increases in tachykinin gene expression, reflecting increased neuronal activity. We have proposed that infundibular neurons containing NKB, SP and estrogen receptor mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback on gonadotropin release in the human. In addition, there is evidence to suggest that the hypertrophied tachykinin neurons may be involved in the initiation of menopausal flushes. Because menopause affects a well characterized system, and has consistent and substantial changes in hormone levels, we have had the rare opportunity to correlate changes in hormone secretion with structural and neurochemical changes in the human hypothalamus. We suspect that future studies of the hypothalami of post-menopausal women will continue to be a fruitful avenue for investigating neuroendocrine regulation in the human.
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PMID:Hormonal influences on morphology and neuropeptide gene expression in the infundibular nucleus of postmenopausal women. 133 3

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Rhesus monkeys (Macaca mulatta) reared during the first year of life without social contact develop persistent stereotyped movements, self-directed behaviors, and psychosocial abnormalities, but neurobiological mechanisms underlying the behaviors of socially deprived (SD) monkeys are unknown. Monkeys were reared in total social deprivation for the first 9 months of life; control monkeys were reared socially (SR) with mothers and peers. Subjects were killed at 19-24 yr of age. Because the behaviors of SD monkeys are reminiscent of changes in striatal or amygdalar function, we used immunocytochemistry for substance P (SP), leucine-enkephalin (LENK), somatostatin, calbindin, and tyrosine hydroxylase (TH) to evaluate qualitatively and quantitatively patterns of neurotransmitter marker immunoreactivity within subcortical regions. In SD monkeys, the chemoarchitecture of the striatum was altered. Neuronal cell bodies and processes immunoreactive for SP and LENK were depleted markedly in patch (striosome) and matrix regions of the caudate nucleus and putamen; the average density of SP-immunoreactive neurons was reduced 58% relative to SR monkeys. Calbindin and TH immunoreactivities were diminished in the matrix of caudate and putamen of SD monkeys. TH-immunoreactive neurons, but not cresyl violet-stained neurons, in the substantia nigra pars compacta were decreased (43%) in SD monkeys. Peptide-immunoreactive terminals were reduced in the globus pallidus and substantia nigra in SD monkeys. The nucleus accumbens was the least affected of striatal regions. Striatal somatostatin immunoreactivity wa qualitatively and quantitatively similar in SD and SR monkeys. Several regions, for example, bed nucleus of the stria terminalis, amygdala, and basal forebrain magnocellular complex, that were in the same sections and are enriched in these markers did not appear altered in SD monkeys, suggesting a regional specificity for vulnerability. The altered chemoarchitecture of some basal ganglia regions in adult monkeys that experienced social deprivation as infants suggests that the postnatal maturation of neurotransmitter phenotypes in some structures is influenced by social environment. Abnormal motor and psychosocial behaviors resulting from this form of social/sensory deprivation may result from alterations in peptidergic and dopaminergic systems within the basal ganglia.
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PMID:Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions. 168 26

Conventional immunoperoxidase preparations of the coronally sectioned brains of rats killed at various times during the early postnatal period revealed the distributions of tyrosine hydroxylase, substance P, and neurotensin immunoreactivities. At birth, patches of dense tyrosine hydroxylase immunoreactivity were present across the breadth of the rostral striatum, whereas patches displaying substance P immunoreactivity were present only in its lateral half, appearing in its medial half by about postnatal day 3. Neuronal neurotensin immunoreactivity was absent in the rostral striatum at birth, although some neurotensin immunoreactive cells were present in the tail of the caudate-putamen. Rostrally, neurotensin immunoreactive cells appeared first along the lateral margin of the caudate-putamen on postnatal day 3, became numerous there about day 5, spread medially into the striatum by day 7, and achieved their medialmost distribution by about day 10. Their numbers and those of substance P immunoreactive neurons diminished thereafter. Substance P immunoreactive patches, which contained numerous labeled neurons and "puncta," shared coextensive distributions with patches of dense tyrosine hydroxylase immunoreactivity, but interdigitated with neurotensin immunoreactive cell clusters. The neurotensin immunoreactive cell clusters lacked puncta, the light microscopic representation of axon terminals, or swellings. It is concluded that the patchy infrastructure of the striatum, which is established prior to birth, is substrate for the progression of separate "waves" of elevated neuronal peptide content, one reflecting substance P and a later one reflecting neurotensin. These proceed along rostromedialward trajectories to involve interdigitating neuronal domains.
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PMID:Postnatal development of striatal neurotensin immunoreactivity in relation to clusters of substance P immunoreactive neurons and the "dopamine islands" in the rat. 169 90

The arrangement of the enteric nerve plexuses in the colon of the guinea-pig and the distributions and projections of chemically specified neurons in this organ have been studied. Immunoreactivity for neuron specific enolase was used to examine the total population of neurons and individual subpopulations were studied using antibodies raised against calbindin, calcitonin gene-related peptide (CGRP), leu-enkephalin, gastrin releasing peptide (GRP), galanin, gamma aminobutyric acid, neurokinin A, neuropeptide Y (NPY), somatostatin, substance P, tyrosine hydroxylase and vasoactive intestinal peptide (VIP). Neuronal pathways within the colon were lesioned using myotomy and myectomy operations and extrinsic pathways running between the inferior mesenteric ganglia and the colon were also severed. Each of the antibodies revealed nerve cells and nerve fibres or only nerve fibres within the wall of the colon. VIP, galanin and GRP were in anally projecting pathways in the myenteric plexus, as they are in other species. In contrast, there are differences in the projection directions of enkephalin, substance P, NPY and somatostatin nerve fibres between regions and species. Surprisingly, somatostatin and NPY fibres have opposite projections in the small intestine and colon of the guinea-pig. The majority of nerve fibres that innervate the circular muscle, including fibres with immunoreactivity for VIP, enkephalin, substance P, NPY, galanin and GRP come from the myenteric ganglia. The mucosa is innervated by fibres from both the myenteric and submucous ganglia. The present results suggest that the guinea-pig distal colon is a suitable place in which to determine relations between structure, neurochemistry and functions of enteric neural circuits.
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PMID:Projections of chemically-specified neurons in the guinea-pig colon. 170 5

Mast cells are involved in allergic reactions where they release numerous vasoactive and other mediators in response to IgE and antigen. They are also activated by neuropeptides and are found in close contact with neurons. Mast cell heterogeneity has now been documented for mucosal mast cells and connective tissue mast cells. Rat brain mast cells were studied in a perfusion system and were shown to release serotonin in response to the mast cell secretagogue compound 48/80 (C48/80). High-potassium neuronal depolarization also released serotonin, but this was calcium dependent, not associated with beta-hexosaminidase, and was unaffected by prior treatment with C48/80. Neuronal depolarization, however, was associated with somatostatin secretion and substantially reduced subsequent C48/80 stimulation, an effect abolished by neonatal treatment of the animals with capsaicin. Perfusion with somatostatin and substance P also induced brain mast cell serotonin release. C48/80 stimulation of combined thalamic and hypothalamic slices after neuronal depolarization substantially reduced the C48/80 effect, suggesting the possible presence of endogenous inhibitors released from the hypothalamus. Finally, the alpha 2-receptor agonist clonidine had a slight stimulatory effect. These results indicate that brain mast cell serotonin release may be regulated by endogenous neurotransmitters and/or neuromodulators.
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PMID:Endogenous regulation of rat brain mast cell serotonin release. 172 Apr 23

The experiments on Wistar rats showed that microinjection of C-terminal fragment of substance P-CP5-11 (1 microgram) into one of the antinociceptive system structure--dorsal raphe nucleus, caused a prolonged (24 hours of observation) analgetic effect by the hot plate test. Neuronal activity of dorsal raphe nucleus simultaneously enhanced. The CP5-11 antinociceptive activity was higher than the CP1-11 one. The conclusion is that CP1-11 and in particular its C-terminal fragment CP5-11 play a role in activation of antinociceptive system.
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PMID:[Effects of C-terminal fragment of substance P-CP 5-11 on the activity of neurons of the dorsal raphe nucleus]. 172 29

Histochemical, immunocytochemical, and radioenzymatic techniques were used to examine the neurotransmitter-related properties of the innervation of thoracic hairy skin in rats during adulthood and postnatal development. In the adult, catecholamine-containing fibers were associated with blood vessels and piloerector muscles, and ran in nerve bundles throughout the dermis. The distribution of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers was identical. Neuronal fibers displaying neuropeptide Y (NPY) immunoreactivity were seen in association with blood vessels. Double-labeling studies suggested that most, if not all, NPY-IR fibers were also TH-IR and likewise most, if not all, vessel-associated TH-IR fibers were also NPY-IR. Calcitonin gene-related peptide (CGRP)-IR fibers were observed near and penetrating into the epidermis, in close association with hair follicles and blood vessels, and in nerve bundles. A similar distribution of substance P (SP)-IR fibers was evident. In adult animals treated as neonates with the sympathetic neurotoxin 6-hydroxydopamine, a virtual absence of TH-IR and NPY-IR fibers was observed, whereas the distribution of CGRP-IR and SP-IR fibers appeared unaltered. During postnatal development, a generalized increase in the number, fluorescence intensity, and varicose morphology of neuronal fibers displaying catecholamine fluorescence, NPY-IR, CGRP-IR, and SP-IR was observed. By postnatal day 21, the distribution of the above fibers had reached essentially adult levels, although the density of epidermal-associated CGRP-IR and SP-IR fibers was significantly greater than in the adult. The following were not evident in thoracic hairy skin at any timepoint examined: choline acetyltransferase activity, acetylcholinesterase histochemical staining or immunoreactivity, fibers displaying immunoreactivity to vasoactive intestinal peptide, cholecystokinin, or leucine-enkephalin. The present study demonstrates that the thoracic hairy skin in developing and adult rats receives an abundant sympathetic catecholaminergic and sensory innervation, but not a cholinergic innervation.
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PMID:Postnatal development of autonomic and sensory innervation of thoracic hairy skin in the rat. A histochemical, immunocytochemical, and radioenzymatic study. 197 33


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