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)

While much evidence implicates substance P (SP), an endogenous neurokinin (NK), as a primary sensory transmitter of acute pain in mammalian spinal cord, its role in continuous (tonic) pain is less clear. Although glutamate is co-localized with SP in dorsal root ganglion neurons, its role in nociceptive processing is uncertain. While antagonists of NKs and excitatory amino acids (EAAs) have been found to be antinociceptive in some acute assays, they have not been tested against tonic pain. We hypothesize that: (1) NKs and EAAs contribute to signaling of tonic chemogenic nociception; and (2) interaction between NK and EAA systems is important in determining the perceived intensity of a continuous noxious stimulus. We therefore evaluated two NK antagonists ([D-Pro2,D-Trp7,9] SP (DPDT-SP, 0.26-6.6 nmoles, non-specific) and [D-Pro4, D-Trp7,9,10,Phe11]-SP(4-11) (DPDTP-octa, 1.6-12.3 nmoles, somewhat NK-1 selective], as well as DL-2-amino-5-phosphonovalerate (DL-AP5, NMDA antagonist, 0.05-1 nmole) and urethane (a kainic acid (KA) antagonist at 2.5 mumoles) for antinociceptive activity in the mouse formalin model. Administered intrathecally (i.t.), DL-AP5 and both NK antagonists were significantly antinociceptive while urethane (2.5 mumoles) and naloxone (2.7 nmoles) were inactive. A50 values for mean % analgesia, nmoles/mouse i.t. (95% CLs) were: DPDT-SP, 1.1 (0.79-1.6); DPDTP-octa, 3.9 (2.4-6.1); DL-AP5, 0.29 (0.16-0.71). The antinociception associated with 1.3 nmoles of DPDT-SP was not reversed by co-administering 2.7 nmoles of naloxone. Co-administration of 0.1 nmoles of DL-AP5 with either 1.3 nmoles of DPDT-SP or 3.3 nmoles of DPDTP-octa did not lead to additive antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurokinin and NMDA antagonists (but not a kainic acid antagonist) are antinociceptive in the mouse formalin model. 171 Nov 93

Recent electrophysiological evidence shows that rostral levels of the trigeminal spinal complex are concerned with pain processing from receptive fields in the face and oral cavity. The ventrolateral quadrant of the subnucleus interpolaris contains concentrations of enkephalin, dynorphin, serotonin, substance P and GABA [Matthews M. A., Hernandez T. V. and Liles S. L. (1987) Synapse 1, 512-529; Matthews M. A., McDonald G. K. and Hernandez T. V. (1988) Somatosensory Res. 5, 205-217]. These transmitters have also been localized to the fusiform and stalked cells in Laminae I and II of the subnucleus caudalis [Basbaum A. I. and Fields H. L. (1984) A. Rev. Neurosci. 7, 309-338]. The present study compares Golgi impregnations of the subnucleus interpolaris with sections at the same levels immunoreacted against enkephalin to determine if comparable cells exist in the subnucleus interpolaris and if they occur predominantly in the ventrolateral quadrant of the subnucleus. Twelve, young adult cats were killed by perfusion, the brainstems removed and either processed for rapid Golgi impregnation or sectioned and immunoreacted for enkephalin using the avidin-biotin Vectastain method. Golgi impregnated tissue was sectioned in the coronal, transverse or sagittal plane to insure the most advantageous visualization of cells with a directional bias in their dendritic arbors. The subnucleus interpolaris contained several distinctive cell types. The predominant neuron throughout the subnucleus was the smooth pyramidal cell or multipolar cell, characterized by a large round soma (15-25 microns diameter) and a spherical dendritic arborization which allowed its identification in all planes of section. The second cell type was the fusiform cell which had a smaller ovoid soma (10-15 microns) with narrow, less ramified, dendritic arbors oriented dorsoventrally, thus giving a bipolar appearance. Fusiform cells were most concentrated along the lateral margin of the subnucleus interpolaris. Examination of sections at the same level reacted for enkephalin revealed cells with a bipolar appearance in these same locations. An additional cell population which tended to predominate in the lateral zone was the stalked cell. These displayed a rounded soma (12-20 microns) and were evident only in the transverse or sagittal plane. Two to four primary dendrites arose from the soma and extensively ramified into a dense spiny arbor directed into the body of the subnucleus interpolaris. Many examples contained enkephalin. Islet cells, characterized by a very small oval soma (6-12 microns) and dense, rostrocaudally oriented dendrites, were less common than stalked cells and were located deeper in the nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Golgi and immunocytochemical analysis of neurons in trigeminal subnucleus interpolaris: correlations with cellular localization of enkephalin. 247 85

Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), beta-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4-5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6-12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease.
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PMID:Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease. 884 73

The present study showed that neural degeneration occurred in the cardiac ganglia after bilateral vagotomy. At 1 week after operation, a majority of the substance P-like immunoreactive (SP-IR) nerve fibres were affected and they showed signs of degeneration. SP-IR nerve endings forming the pericellular baskets around seemingly normal neuronal cell bodies were also degenerated. By 2 weeks after operation, numerous macrophage-like cells infiltrated the cardiac ganglia and they engulfed the degenerating SP-IR cellular debris. At 3 months after operation, a few fine SP-IR nerve fibres were detected in the cardiac ganglia, together with a few small solitary SP-IR neurons. At 6-12 months after operation, numerous SP-IR nerve fibres were observed in the cardiac ganglia. Some of the SP-IR nerve endings started to form pericellular baskets around the seemingly normal neuronal cell bodies. It is concluded that there is reinnervation of the heart by SP-IR nerve fibres after surgical interruption to both vagi. However, the origin of these SP-IR nerve fibres and terminals remains unknown.
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PMID:The effects of bilateral vagotomy on substance P-like immunoreactive nerves in the cardiac ganglia of the monkey (Macaca fascicularis). 905 24

The mas-related genes (Mrgs, also known as sensory neuron-specific receptors, SNSRs) are specifically expressed in small diameter sensory neurons in the trigeminal and dorsal root ganglia, suggesting an important role of the receptors in pain transmission. The present study aimed to investigate the underlying mechanism of the nociceptive effects after activation of MrgC, and the interaction between MrgC and N/OFQ-NOP receptor system in modulation of nociception in mice. Intrathecal (i.t.) administration of [Tyr(6)] gamma2-MSH(6-12), the most potent agonist for MrgC receptor, produced a significant hyperalgesic response as assayed by tail withdrawal test and a series of characteristic nociceptive responses, including biting, licking and scratching, in a dose-dependent manner (0.01-10 pmol and 0.01-10 nmol, respectively) in mice. These pronociceptive effects induced by [Tyr(6)] gamma2-MSH(6-12) were inhibited dose-dependently by co-injection of competitive NMDA receptor antagonist D-APV, non-competitive NMDA receptor antagonist MK-801, and nitric oxide (NO) synthase inhibitor L-NAME. However, the tachykinin NK(1) receptor antagonist L-703,606, and tachykinin NK(2) receptor antagonist MEN-10,376, had no influence on pronociceptive effects elicited by [Tyr(6)] gamma2-MSH(6-12). In other groups, [Tyr(6)] gamma2-MSH(6-12)-induced nociceptive responses were bidirectionally regulated by the co-injection of N/OFQ. N/OFQ inhibited nociceptive responses at high doses (0.01-1 nmol), but potentiated the behaviors at low doses (1 fmol-3 pmol). Furthermore, both hyperalgesia and nociceptive responses were enhanced after the co-administration with NOP receptor antagonist [Nphe(1)]N/OFQ(1-13)-NH(2). These results suggest that intrathecal [Tyr(6)] gamma2-MSH(6-12)-induced pronociceptive effects may be mediated through NMDA receptor-NO system in the spinal cord, and demonstrate the interaction between MrgC and N/OFQ-NOP receptor system in pain transmission.
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PMID:Involvement of NMDA receptor in nociceptive effects elicited by intrathecal [Tyr6] gamma2-MSH(6-12), and the interaction with nociceptin/orphanin FQ in pain modulation in mice. 1933 41