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)

Carcinoid tumors of the middle ear are rare, with only three previously reported cases. The authors report the light and electron microscopic and immunohistochemical features of two carcinoid tumors that occurred in a 34-year-old female and a 21-year-old male. Both presented with unilateral hearing loss. By light microscopic examination, both were characterized by trabecula of tall columnar cells with basal nuclei and no mitotic activity. Electron microscopic examination demonstrated large numbers of pleomorphic neurosecretory granules, perinuclear aggregates of intermediate filaments, cell junctions, and surface microvillous processes. Some cells contained intermediate filaments forming tonofilaments and lacked secretory granules. These cells stained for cytokeratin by immunoperoxidase and separated the neuroendocrine cells from the underlying basal lamina. The cells in this tumor stained for the molluscan cardioexcitatory peptide. Cells in both tumors also stained for pancreatic polypeptide. Neither case stained for lysozyme, insulin, glucagon, somatastatin, gastrin, substance P, thyroid-stimulating hormone, adrenocorticotropic hormone, Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, neurotensin, Bombesin, serotonin, neuron-specific enolose, glial and neural filaments, S-100 protein, cholecystokinin, beta-endorphin, beta-human chorionic gonadotropin, luteinizing hormone/follicle-stimulating hormone, vasoactive intestinal polypeptide, prolactin or calcitonin. Carcinoid tumor of the middle ear can be distinguished from paraganglioma and middle ear adenoma.
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PMID:Carcinoid tumors of the middle ear. 357 33

Neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), lysyl-bradykinin, somatostatin, Met- and Leu-enkephalin were tested for their smooth muscle activity in isolated human mesenteric arteries and veins. Only NPY regularly contracted both arteries and veins. Alpha-adrenergic and 5-HT2 antagonists did not affect the response. Somatostatin contracted the veins, but not the arteries, in a variable but concentration-dependent way. The other neuropeptides were without contractile effect. CGRP, bradykinin, and SP regularly dilated, in a concentration-dependent way, both arteries and veins precontracted with prostaglandin F2 alpha or uridine triphosphate. CGRP and bradykinin were the most potent dilators. VIP and somatostatin usually caused a moderate dilatation in the arteries, whereas in the veins, somatostatin was without dilatory effect and the VIP-induced dilatation was irregular. In both types of vessels Met-enkephalin seldom gave any significant dilatation, and no response occurred in the presence of Leu-enkephalin or NPY. The SP-antagonist (D-Arg, D-Trp, Leu)-SP (spantide) caused a dextal shift of the concentration-response curves for SP, in the case of the arteries also including a reduced maximum effect.
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PMID:Contractile and dilatory action of neuropeptides on isolated human mesenteric blood vessels. 358 45

The causative factors underlying SIDS are still unknown, but in recent years much interest has been focused on the central ventilatory control system. In this study, peptides which are known to affect respiration were examined in brains from SIDS victims and controls. The levels of Met-enkephalin and substance P were measured in cortex, medulla oblongata, pons and hypothalamus. Substance P1-7, substance P C-terminal fragments, Met-enkephalin-Lys6 and neuropeptide Y (NPY) were estimated in medulla oblongata. The substance P levels in the medulla oblongata from the SIDS victims were significantly elevated compared with the controls. No change, however, was observed in the Met-enkephalin levels, but a tendency to higher levels in the youngest infants was noticed. As substance P and enkephalins have opposite effects on respiration, their relative concentrations were calculated in each individual sample. The ratio was significantly higher in the medulla oblongata from the SIDS victims. The levels of NPY, substance P1-7, C-terminal fragments of substance P and Met-enkephalin-Lys6 were similar in both groups. A significant correlation between the NPY levels and age was observed, however.
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PMID:Post-mortem analyses of neuropeptides in brains from sudden infant death victims. 608 39

The effects of methionine5-enkephalin (Met-enkephalin, ME) 5 X 10(-8)-5 X 10(-6) moll-1) were investigated on the resting guinea-pig ileum. While in contact with the ileum, ME reduced the natural tone and movements, but following washout a contracture occurred which increased with increasing duration of the contact period from 0.5 to 32 min and with increasing concentration of the ME present during the contact period. The washout contractures after 2 min contact with ME, 10(-6) moll-1, were abolished by naloxone, 10(-6)moll-1, added prior to the addition of ME, atropine, 5 X 10(-6)moll-1 and the substance P (SP) antagonist, (D-Pro2, D-Phe7, D-Trp9)-SP, 10(-5)moll-1 and were reduced by 5-hydroxytryptamine (5-HT)-autodesensitization. Washout contractures following 32 min contact with ME, 10(-6)moll-1, were significantly inhibited by the SP antagonist and naloxone and were abolished by a combination of atropine and the SP antagonist, but were not significantly reduced by atropine alone or by 5-HT-desensitization. Contractures of ileum occurred on addition of naloxone to ileal segments exposed to ME for 2 or 32 min. These contractures were also inhibited by the SP antagonist but a combination of atropine and SP-desensitization was required to abolish them. It was concluded that gut dependence occurs following very brief exposure to an opioid and that SP plays a central role in the withdrawal response precipitated either by washout or addition of naloxone.
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PMID:Contracture of guinea-pig ileum on withdrawal of methionine5-enkephalin is mediated by substance P. 608 49

Parkinson's disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.
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PMID:Brain neurotransmitters and neuropeptides in Parkinson's disease. 609 88

[125I]Iodo-Tyr1-somatostatin (SRIF) binds with high affinity to one class of sites in the rat anterior pituitary with a KD of 0.91 +/- 0.22 nM and a receptor concentration of 104.4 +/- 1.9 fmol/mg protein. This binding is saturable with respect to tissue concentration and is time-, temperature-, pH-, and calcium-dependent. It is also reversible as a function of time. The rates of association and dissociation were calculated to be 5.98 X 10(7) M-1 min-1 and 0.578 min-1, respectively. Binding of [125I]iodo-Tyr1-SRIF is not inhibited by morphine, beta-endorphin, [D-Ala2]Met-enkephalin, LHRH, TRH, histidylproline diketopiperazine, neurotensin, substance P, bombesin or vasoactive intestinal peptide. In contrast SRIF, [Tyr1]SRIF, and [D-Trp8,D-Cys14]SRIF displace [125I]iodo-Tyr1-SRIF binding with Ki values 0.10 +/- 0.05, 0.46 +/- 0.18, 0.05 +/- 0.01 nM, respectively. The constants of inhibition of a series of alanine monosubstituted analogs of SRIF are correlated (r = 0.89) with their biological potency on GH secretion. Furthermore, postnatal development patterns of [125I]iodo-Tyr1-SRIF binding sites follow the ability of SRIF to inhibit GH release. Thus, [125I]iodo-Tyr1-SRIF binding to adenohypophyseal membranes seems to reflect interaction with SRIF receptors on adenohypophyseal cells. Since biological effects of the peptide have been reported on GH, thyrotropin-stimulating hormone, and PRL secretion, further studies are required to determine the cell types upon which this binding occurs.
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PMID:Somatostatin receptors on rat anterior pituitary membranes. 612 57

To clarify whether various neuropeptides found in the hypothalamus act directly on a pituitary adenoma causing Nelson's syndrome, we examined the influence of these peptides on the secretion of immunoreactive ACTH, beta-endorphin, and melanotropins, the proopiomelanocortin (POMC)-derived peptides, by the cultured pituitary adenoma from a patient with Nelson's syndrome. Results showed that somatostatin-14 and somatostatin-28 suppressed the secretion of POMC-derived peptides by the adenoma and that somatostatin-28 was as potent as somatostatin-14. Other neuropeptides such as arginine vasopressin, vasoactive intestinal polypeptide, and oxytocin stimulate the secretion of POMC-derived peptides. Substance P, TRF, Met-enkephalin and Leu-enkephalin were also found to modulate the secretion of POMC-derived peptides. This suggests that the adenoma may have multiple receptors to various neuropeptides.
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PMID:Effects of various neuropeptides on the secretion of proopiomelanocortin-derived peptides by a cultured pituitary adenoma causing Nelson's syndrome. 612 87

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 transmitters contained in the efferent projections of the striatum were studied by producing two types of lesions: coronal hemitransections just anterior to the globus pallidus, and semi-circular knife cuts that isolated a considerable portion of the globus pallidus from the striatum to produce 'GP islands'. The levels of substance P and Met-enkephalin in the globus pallidus, entopeduncular nucleus and substantia nigra were measured after these lesions. For comparison, the effect of these lesions on glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) in some of these projection areas of the striatum was assessed. Both lesions caused similar reductions in substance P levels in each of the three striatal projection areas. In contrast, hemitransections reduced Met-enkephalin levels only in the globus pallidus. Both lesions reduced pallidal and entopeduncular GAD activity while nigral GAD activity was reduced only by the hemitransections. CAT activity was reduced in the globus pallidus by both lesions but was unaltered in the entopeduncular nucleus. However, additional experiments ruled out the existence of a striato-pallidal cholinergic projection. GAD activity and Met-enkephalin levels were significantly increased in the striatum anterior to the lesions. In contrast, CAT activity and substance P levels did not change in this region. The results support and broaden emerging view of the organization of the neurons containing the various transmitter candidates of the efferent projections of the striatum.
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PMID:Neurotransmitters contained in the efferents of the striatum. 615 76

The release of transmitters was studied in various structures of the basal ganglia in cats implanted with several push-pull cannulas. Local depolarization enhanced Met-enkephalin release in the globus pallidus. Activation of striatonigral substance P(SP) neutrons stimulated the transmitter release from terminals. Unilateral electrical stimulation of the caudate nucleus evoked GABA release in both substantia nigrae and pallidoentopeduncular nuclei. The unilateral facilitation or interruption of nigral SP transmission modified dopamine (DA) release in the ipsilateral caudate nucleus in contrast, modifications of GABAergic or glycinergic nigral transmissions induced bilateral symmetrical effects, whereas bilateral asymmetrical changes in DA release in the two caudate nuclei were seen during the unilateral modification of nigral DA transmission. Changes in the dendritic release of DA induced changes in serotonin release both in the substantia nigra and in the ipsilateral caudate nucleus. Finally, it will be shown that acetylcholinesterase can be released from the substantia nigra and the caudate nucleus through processes dependent on nerve activity.
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PMID:In vivo release of transmitters in the cat basal ganglia. 616 43


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