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 expression of 34 transmitter-related genes has been examined in the cholinergic neurones of rat striatal brain slices, with the aim of correlating gene expression with functional activity. The mRNAs encoding types I, II/IIA, and III alpha subunits of the voltage-sensitive sodium channels were detected, suggesting the presence of these three types of sodium channel. Similarly, mRNAs encoding all four alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-type glutamate receptor subunits and the NR1 and NR2A, 2B, and 2D subunits of the NMDA-type glutamate receptors were detected, suggesting that various combinations of these subunits mediate the cellular response to synaptically released glutamate. Other mRNAs detected included the NK1 and NK3 tachykinin receptors, all four known adenosine receptors, and the GABA-synthesising enzyme glutamate decarboxylase. Subpopulations of these cholinergic neurones have been identified on the basis of the expression of the NK3 tachykinin receptor in 5% and the trkC neurotrophin receptor in 12% of the cells investigated.
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PMID:Correlating physiology with gene expression in striatal cholinergic neurones. 1064 37

We have investigated the ability of protease-activated receptor-1 (PAR-1), PAR-2, PAR-3 and PAR-4 agonists to induce contractile responses in isolated guinea-pig gallbladder. Thrombin, trypsin, mouse PAR-1 activating (SFLLRN-NH(2)) peptide, and mouse PAR-2 activating (SLIGRL-NH(2)) and human PAR-2 activating (SLIGKV-NH(2)) peptides produced a concentration-dependent contractile response. Mouse PAR-4 activating (GYPGKF-NH(2)) peptide, the mouse PAR-1 reverse (NRLLFS-NH(2)) peptide, the mouse PAR-2 reverse (LRGILS-NH(2)) and human PAR-2 reverse (VKGILS-NH(2)) peptides caused negligible contractile responses at the highest concentrations tested. An additive effect was observed following the contractile response induced by either trypsin or thrombin, with the addition of a different PAR agonist (SFLLRN-NH(2) and SLIGRL-NH(2), respectively). Desensitization to PAR-2 activating peptide attenuated the response to trypsin but failed to attenuate the response to PAR-1 agonists, and conversely desensitization to PAR-1 attenuated the response to thrombin but failed to alter contractile responses to PAR-2 agonists. The contractile responses produced by thrombin, trypsin, SFLLRN-NH(2) and SLIGRL-NH(2) were markedly reduced in the presence of the cyclo-oxygenase inhibitor, indomethacin, whilst the small contractile response produced by NRLLFS-NH(2) and LRGILS-NH(2) were insensitive to indomethacin. The contractile responses to thrombin, trypsin, SFLLRN-NH(2) and SLIGRL-NH(2) were unaffected by the presence of: the non-selective muscarinic antagonist, atropine; the nitric oxide synthase inhibitor, L-NAME; the sodium channel blocker, tetrodotoxin; the combination of selective tachykinin NK(1) and NK(2) receptor antagonists, (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2] octane chloride (SR140333) and (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3, 4-dichlorophenyl)-butyl] benzamide (SR48968), respectively. The results indicate that PAR-1 and PAR-2 activation causes contractile responses in the guinea-pig gallbladder, an effect that is mediated principally by prostanoid release, and is independent of neural mechanisms.
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PMID:Evidence that PAR-1 and PAR-2 mediate prostanoid-dependent contraction in isolated guinea-pig gallbladder. 1103 Jul 17

We sought to determine the capacity of ventricular sensory nerve endings (neurites) associated with neonatal nodose ganglion afferent neurons to transduce mechanical and chemical stimuli in situ. Spontaneous activity generated by 17 nodose ganglion cardiac afferent neurons was identified in 8 anesthetized neonatal pigs (10-21 days old) using extracellular recording recording techniques. The activity generated by afferent neurons was studied when their ventricular sensory neurites were exposed to local mechanical or chemical stimuli, following systemic administration of specific chemicals or during brief periods of apnea. Gentle mechanical distortion of their ventricular sensory fields enhanced the activity generated by 6 spontaneously active afferent neurons, while suppressing the activity generated by another 3 neurons. Afferent neuronal activity was either enhanced or suppressed when the following chemicals were applied to identified ventricular epicardial sensory fields: the sodium channel modifier veratridine (92% of tested neurons); the P1-purinoceptor agonist adenosine (92%); the neuropeptides angiotensin II (100%), bradykinin (90%) and substance P (90%); and the nitric oxide donor S-nitroso-N-acetylpenicillamine (100%). Epicardial application of isoproternol or nicotine induced modest neuronal responses. Cardiac afferent neurons were also affected when these chemicals were administered systemically. Apnea of 60-100 s duration modified (enhanced, n = 2; suppressed, n = 5) the activity generated by most identified afferent neurons. The estimated average conduction velocity of afferent axons associated with these neurons was 1.0 +/- 0.2 m/s. It is concluded that neonatal nodose ganglion cardiac afferent neurons respond to many of the chemicals known to modify adult cardiac afferent neurons. That cardiac afferent neurons are capable of sensing the mechanical and chemical milieu of the neonatal heart should be taken into account when considering altered neonatal cardiovascular status such as occurs during apnea.
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PMID:Transduction capabilities of neonatal ventricular afferent neurons in vivo. 1127 Jan 37

The skin surface electric potential has been widely used for psychological studies because it is sensitive to emotional conditions. We measured the electric potential on the surface of hairless mice skin in organ culture with several physiological factors. Disruption of mitochondrial function and inhibition of ATPase reduced the skin surface potential 50-70%. Calcium, potassium, and sodium channel blockers also reduced the potential. A calcium-specific and potassium ionophore reduced the potential, but the calcium and magnesium ionophore increased it. EDTA decreased the potential but EGTA had no effect. Skin surface barrier disruption reduced the potential and calcium and potassium channel blockers partially prevented the decrease. Substance P and corticotropin-releasing factor decreased the potential, and antagonists blocked the decreases. These results suggest that the ion flux in the nucleated layer of the epidermis induce the skin surface potential and it is influenced by environmental and neuroendocrinological factors.
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PMID:Skin surface electric potential induced by ion-flux through epidermal cell layers. 1137 79

Many known painkillers are not always effective in the therapy of chronic neuropathic pain manifested by hyperalgesia and tactile allodynia. The mechanisms underlying neuropathic pain appear to be complicated and to differ from acute and inflammatory pain. Recent advances in pain research provide us with a clear picture for the molecular mechanisms of acute pain, and substantial information is available concerning the plasticity that occurs under conditions of neuropathic pain. The most important changes responsible for the mechanisms of neuropathic pain are found in the altered gene/protein expression in primary sensory neurons. After damage to peripheral sensory fibers, up-regulated expression of the Ca(v)alpha(2)delta-(1) channel subunit, the Na(v)1.3 sodium channel, and bradykinin (BK) B1 and capsaicin TRPV1 receptors in myelinated neurons contribute to hyperalgesia; while the down-regulation of the Na(v)1.8 sodium channel, B2 receptor, substance P (SP), and even mu-opioid receptors in unmyelinated neurons is responsible for the phenotypic switch in pain transmission. Clarification of the molecular mechanisms for such complicated plasticity would be extremely valuable when considering the therapeutic design of pain relieving drugs. Although many reports deal with the changes in expression of key molecules related to neuropathic pain, the initiation and the mechanisms that follow remain to be determined. The current study using lysophosphatidic acid (LPA) receptor knockout mice revealed that LPA produced by nerve injury initiates neuropathic pain and demyelination following partial sciatic nerve ligation (PSNL). A single injection of LPA was found to mimic PSNL in terms of neuropathic pain and its underlying mechanisms. This discovery may lead to the subsequent discovery of LPA-induced secondary genes, which would be therapeutic targets for neuropathic pain.
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PMID:Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. 1602 29

Tree frogs produce a variety of skin defensive chemicals against many biotic and abiotic risk factors for their everyday survival. By proteomics or peptidomics and coupling transcriptome analysis with pharmacological testings, 27 peptides or proteins belonging to 9 families, which act mainly as defensive functions, were identified and characterized from skin secretions of the tree frog, Hyla simplex. They are: (1) a novel family of peptides with EGF- and VEGF-releasing activities; (2) a novel family of analgesic peptides; (3) a family of neurotoxins acting on sodium channel; (4) a snake venom-like presynaptically active neurotoxin; (5) a snake venom-like neurotoxin targeting cyclic nucleotide-gated ion channels; (6) a tachykinin-like peptide, which is the first report from tree frogs; (7) two antimicrobial peptides; (8) a alpha-1-antitrypsin-like serpin; and (9) a wasp venom-like toxin with serine protease inhibitors activity. Families of 1, 2, 4, 5, and 8 proteins or peptides are first reported in amphibians. The chemical array in the tree frog skin shares some similarities with snake venoms. Most of these components in this tree frog help defend against predators, heal wounds, or attenuate suffering.
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PMID:Proteomic analysis of skin defensive factors of tree frog Hyla simplex. 2174 67

Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.
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PMID:Current and Future Issues in the Development of Spinal Agents for the Management of Pain. 2686 70

Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, because xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Because the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose dependently increased the rate of duodenal HCO3- secretion in perfused duodenal loops of anesthetized rats. Xenin was immunolocalized to a subset of enteroendocrine cells in the rat duodenum. The mRNA of the xenin/NT receptor 1 (NTS1) was predominantly expressed in the enteric plexus, nodose and dorsal root ganglia, and in the lamina propria rather than in the epithelium. The serosal application of xenin-8 or xenin-25 rapidly and transiently increased short-circuit current in Ussing-chambered mucosa-submucosa preparations in a concentration-dependent manner in the duodenum and jejunum, but less so in the ileum and colon. The selective antagonist for NTS1, substance P (SP) receptor (NK1), or 5-hydroxytryptamine (5-HT)3, but not NTS2, inhibited the responses to xenin. Xenin-evoked Cl- secretion was reduced by tetrodotoxin (TTX) or capsaicin-pretreatment, and abolished by the inhibitor of TTX-resistant sodium channel Nav1.8 in combination with TTX, suggesting that peripheral xenin augments duodenal HCO3- and Cl- secretion through NTS1 activation on intrinsic and extrinsic afferent nerves, followed by release of SP and 5-HT. Afferent nerve activation by postprandial, peripherally released xenin may account for its secretory effects in the duodenum.
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PMID:Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways. 2811 52


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