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)

The developing fetal monkey visual cortex was studied immunocytochemically from 110-155 days post-conception in order to localize cell populations immunoreactive (ir) for gamma-aminobutyric acid, Substance P, cholecystokinin-octapeptide, somatostatin, neuropeptide Y, and proenkephalin A peptide (BAM-18). The area 17/18 border and all cortical laminae identified in the adult visual cortex were discernible from the youngest age examined. All ir-cell populations studied were present at each fetal age. However, despite a relatively adult-like cytoarchitecture, all ir-cell populations studied displayed patterns of immunostaining which were unlike those described in adult visual cortex, and showed significant changes in laminar distribution, morphology, and numbers over the time course of gestation examined. Despite the differences in the patterns of immunostaining between the fetal and adult visual cortex, ir-cell populations intrinsic to the developing visual cortex exhibited adult-like combinations of co-localized transmitters and peptides. The developing monkey cortex also contains ir-cell populations, particularly BAM-18-ir cells, which have not been detected immunocytochemically in the adult monkey cortex. Differences between the fetal and the adult ir-cell populations might be accounted for by cell death, morphological transformation, secondary migration or changes in gene expression for neurotransmitters and neuropeptides.
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PMID:Temporal sequence of neurotransmitter expression by developing neurons of fetal monkey visual cortex. 246 14

The effects of vasoactive intestinal peptide (VIP) and substance P (SP) on the amount of proenkephalin A (ProEnk A) mRNA in cultures of bovine adrenal chromaffin cells were examined. Exposure of chromaffin cells to 5 microM VIP for 24 h produced a significant elevation in ProEnk A mRNA. The stimulatory effect of VIP could be abolished by the presence of the calcium channel blocker D600 or actinomycin D but was not affected by the nicotinic antagonist hexamethonium. The results suggest that VIP may induce transcription of ProEnk A mRNA by a Ca2+-dependent, non-cholinergic mechanism. By contrast, SP (5 microM) had no effect on the amount of ProEnk A mRNA. Since VIP is found in nerve terminals and the ganglion cells within the adrenal medulla, this peptide could be an endogenous regulator of adrenal enkephalin gene expression.
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PMID:Vasoactive intestinal peptide stimulates proenkephalin A mRNA expression in bovine adrenal chromaffin cells. 247 28

The monoaminergic innervation of the central nervous system (CNS) is characterized by long and short projecting neurons. The neurological correlates of diabetes are usually referred to as processes of degenerative atrophy affecting motor and sensory peripheral nerves. We have found that the long serotoninergic axons innervating the spinal cord and the cerebral cortex are unaffected in diabetic animals and that the noradrenergic innervation of the cortex is normal as well. The serotonin content is doubled in the hypothalamus with no apparent alteration of 5-HIAA levels, suggesting a supernumerary innervation that is accompanied by a reduced release. In pons medulla oblongata, serotonin and dopamine with the relative metabolites 5-HIAA and DOPAC are significantly reduced, whereas noradrenaline is markedly increased. In the hippocampus, there is a reduction of serotonin content. The serotoninergic alterations are peculiar as suggested by the sparing of the most distal projections that is accompanied by hyperinnervation of the hypothalamus and the loss of shorter collaterals in the pons medulla oblongata. In the hypothalamus and in the striatum of diabetic rats, there are significant higher levels of substance P and met-enkephalin, respectively. The abundance of proenkephalin A mRNA is also increased in the striatum. Conversely, in the lumbar cord of diabetic animals, the levels of substance P and met-enkephalin are significantly reduced. Such alterations likely reflect retrograde degeneration of the peripheral sensory input. The CNS changes are unlikely due to vascular abnormalities in the brain of diabetic rats; rather, we suggest that the persistent lack of insulin is the major factor involved as a trigger of the monoaminergic changes in the diabetic brain.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals. II. Monoaminergic and peptidergic alterations in the diabetic encephalopathy. 248 Apr 54

Current investigations on the immunohistochemical occurrence and co-occurrence of biogenic polypeptides in the mammalian carotid body were reviewed and extended by our own recent findings. The family of chromogranins and related peptides in glomus cells appears to have a widespread interspecies distribution, whereas other peptides investigated occur in a species-specific pattern. Immunoreactivity to antisera against opioids, which derive from the proenkephalin sequence, appears to be present in glomus cells of the rabbit, cat, dog, and a shrew. Conversely, glomus cells of pig and guinea pig predominantly are immunoreactive to cleavage products of prodynorphin, which co-occur in some cells with substance P and met-enkephalin-arg-phe, respectively. In the rat and Callithrix jacchus, opioid immunoreactivity is present in nerve fibres but not in glomus cells. Immunoreactivity to other peptides, such as neurotensin, cholecystokinin, neuropeptide Y, and galanin, is found only in one or two particular species. Neurotensin immunolabelling occurs in beagle dog glomus cells, which are known to lack substance P. Cholecystokinin immunoreactivity is present in glomus cells of dog and Callithrix, and co-exists with chromogranin A, neuropeptide Y, and substance P. Substance P appears to exist in both carotid body glomus cells and nerve fibres. Substance P immunoreactivity is present in glomus cells of all species investigated, except dog. Coexistence of substance P and calcitonin gene-related peptide (CGRP) is demonstrated in nerve fibres of the guinea pig carotid body, which originate in the petrosal and jugular ganglia. Other peptides visualized immunohistochemically in mammalian carotid body nerve fibres are vasoactive intestinal peptide and neuropeptide Y. The functional significance of the various peptides present in the carotid body is discussed.
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PMID:Immunohistochemical distribution and colocalization of regulatory peptides in the carotid body. 267 3

Smooth muscle cells isolated separately from the longitudinal and circular muscle layers of guinea pig and human intestine exhibited a unique pattern of response to derivatives of proenkephalin and prodynorphin present in the myenteric plexus. Receptors for other myenteric transmitters (acetylcholine, the octapeptide of cholecystokinin and substance P) capable of mediating contraction, were present on both circular and longitudinal muscle cells, whereas opiate receptors were present on circular muscle cells and selectively absent from longitudinal muscle cells in both species. The opiate myoreceptors belonged to the three main subclasses (kappa, delta and mu) and exhibited a rank order of sensitivity similar to that of opiate neuroreceptors. The distribution of these receptors parallels the distribution of opioid nerve fibers and appears to reflect the role of opioids in the regulation of neuromuscular activity.
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PMID:Selective presence of opiate receptors on intestinal circular muscle cells. 286 24

Carboxypeptidase H is one of several enzymes required for the processing of peptide hormone precursors. In this study, inhibition of carboxypeptidase H by its peptide products was investigated. Carboxypeptidase H activity in bovine adrenal medulla chromaffin granules and rat adrenal medulla homogenate was inhibited by the peptides Met- and Leu-enkephalin, vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone, with oxytocin and ACTH 1-14 having the least effect, at concentrations of 2-20 mM. Inhibition by amidated peptide products (vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone) show that the final products of the precursor processing pathway can regulate carboxypeptidase H. These levels of peptides are similar to known intragranular peptide concentrations indicating that product and feedback inhibition of carboxypeptidase H may play a role in the control of neuropeptide synthesis. The proenkephalin-derived peptides Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin-Arg6-Phe7 competitively inhibited bovine and rat carboxypeptidase H with Ki values of 12.0, 6.5, 7.0, and 5.5 mM, respectively. The significantly greater Ki for Met-enkephalin may reflect the effects of higher intragranular concentration of Met-enkephalin, since one proenkephalin molecule contains four copies of Met-enkephalin and only one copy of each of the other enkephalin peptides. Thus, the products from one multivalent precursor molecule may equivalently inhibit carboxypeptidase H activity. Product inhibition of carboxypeptidase H and perhaps other processing enzymes may serve to limit the maximum peptide concentration within the secretory vesicle.
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PMID:Product inhibition of carboxypeptidase H. 288 69

The parabrachial nucleus (PB) is the major relay for ascending visceral afferent information from the nucleus of the solitary tract to the forebrain. We have recently found that PB in the rat also receives a substantial afferent projection from neurons in the marginal zone of the entire length of the spinal and trigeminal dorsal horn. Immunoreactive perikarya stained with antisera against several neuropeptides--including dynorphin, enkephalins, and substance P--have been identified in the marginal zone. We therefore investigated the chemical specificity of the spinoparabrachial projection by combining fluorescent retrograde tracing with immunofluorescence for substance P, dynorphin A1-17, met-enkephalin, and two enkephalin precursor fragments (proenkephalin 192-203 and peptide E). Following PB injections of fluorescent dyes, about half of the retrogradely labeled neurons in the marginal zone stained with antisera against either dynorphin or enkephalin series peptides. Elution-restaining experiments indicated that the dynorphin- and enkephalin-immunoreactivities were contained within separate populations of marginal zone neurons. We could not identify any substance P-immunoreactive perikarya in the marginal zone, but substance P-immunoreactive fibers were seen in close apposition to retrogradely labeled, opioid-immunoreactive cell bodies and dendrites. These results indicate that the dynorphin- and enkephalin-immunoreactive perikarya in the marginal zone of the dorsal horn represent independent neuronal populations. These opioid-immunoreactive neurons, which are believed to have extensive local collateral connections, are the main source of a long ascending projection to the parabrachial nucleus in the rat. Furthermore, opioid neurons in the marginal zone may receive substance P-immunoreactive primary sensory afferents.
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PMID:Opioid peptide immunoreactivity in spinal and trigeminal dorsal horn neurons projecting to the parabrachial nucleus in the rat. 301 10

Immunohistochemistry of peptide- and dopamine-beta-hydroxylase-(DBH)-containing varicose nerve fibres and ganglion cells, respectively, in the guinea pig inferior mesenteric ganglion was investigated following a) transsection of mesenteric (colonic) branches, b) transsection of central (lumbar splanchnic, intermesenteric and hypogastric) branches, and c) transplantation into the spleen. The findings indicate that pathways of different opioid peptides are not identical. Met-enkephalin- and met-enkephalin-arg-phe- (cleavage products from pre-proenkephalin) containing fibres course in central branches to make contact in the inferior mesenteric ganglion. Dynorphin- and alpha-neo-endorphin- (deriving from pre-prodynorphin) containing fibres as well as leu-enkephalin- (included in the dynorphin sequence) fibres appear to rise not only from central and from enteric somata, but also from intraganglionic noradrenergic neurons. Similar pathways seem to be used by VIP- and by neurotensin-immunoreactive fibres, although intraganglionic neurotensin-immunoreactive cell bodies are rare. Practically all substance P- and most CGRP-immunoreactive fibres enter the ganglion via central branches and, to a large extent, traverse it, but some CGRP-immunoreactive influx appears to come from the intestine. The origin of intraganglionic substance P- and CGRP-immunoreactive fibres after ganglion transplantation remained unidentified. Somatostatin- and neuropeptide Y-immunoreactive fibres predominantly have an intraganglionic origin as have DBH-immunoreactive noradrenergic fibres. The demonstrated alterations in neuropeptide immunoreactivity of intraganglionic and periganglionic nerve fibres following the applied transsection procedures contribute to the present knowledge on origin and destination of peptidergic transmitter segments in the guinea pig inferior mesenteric ganglion. Moreover, the present study provides evidence that intrinsic participation in intraganglionic fibre supply is more extensive than hitherto believed.
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PMID:Immunohistochemistry of biogenic polypeptides in nerve cells and fibres of the guinea pig inferior mesenteric ganglion after perturbations. 336 35

A motor disorder similar to idiopathic Parkinson's Disease develops in rhesus monkeys after several daily repeated doses of N-methyl-4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP). The concentrations of peptides derived from proenkephalin A, proenkephalin B, substance P and somatostatin were measured by specific radioimmunoassays in the basal ganglia of MPTP-treated monkeys. In MPTP-treated monkeys, dynorphin B concentration was reduced in the caudate. In the putamen, the concentrations of peptides derived from both proenkephalin A and proenkephalin B were decreased. In the globus pallidus, the concentrations of all opioid peptides tend to be increased, reaching significance only for alpha-neo-endorphin. In the substantia nigra, only Met-enkephalin concentration was reduced, while other peptides derived from either proenkephalin A or proenkephalin B were not changed. Substance P and somatostatin were not changed in any brain area examined. Some of the symptoms associated with Parkinson's Disease may be related to altered activity of endogenous opiates in basal ganglia.
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PMID:Primate model of Parkinson's disease: alterations in multiple opioid systems in the basal ganglia. 615 Jul 50

The dynorphin A (1-17), Met-enkephalin-Arg6-Phe7 and substance P levels were determined by RIA following Sep-Pak separation in the striatum, hippocampus and spinal cord of three strains of mice (C57Bl10/D1, A/Sn, A. CA). The C57Bl10/D1 mice had high consumption of 10% ethanol at free choice schedule, whereas the A/Sn and A. CA mice had very low one. The Met-enkephalin-Arg6-Phe7 level was found to be decreased only in the spinal cord and striatum of C57Bl10/D1 mice. It is suggested that decreased synthesis or processing of the proenkephalin may at least partly determine the high level of ethanol consumption by this strain of mice.
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PMID:[The content of dynorphin, Met-enk-Arg6-Phe7 and substance P (1-11) in the brain of mice with different levels of ethanol consumption]. 750 73


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