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)

Transient receptor potential ion channel of the vanilloid type 1 (TRPV1)-dependent pathway, consisting of capsaicin-sensitive tachykininergic primary afferent and myenteric nitrergic neurons, has been suggested to mediate the inhibitory effect of capsaicin on vagally mediated striated muscle contractions in the rat esophagus. In a recent study, similar but also different effects of capsaicin and piperine on TRPV1 were demonstrated. Therefore, this study aimed to compare the effects of these two drugs on vagally induced contractions in the mouse esophagus. Capsaicin and piperine inhibited vagally induced contractions of a thoracic esophageal segment in a concentration-dependent manner. Ruthenium red (10 microM; a non-selective blocker of transient receptor potential cation channels) and SB-366791 (10 microM; a novel selective antagonist of TRPV1) blocked the inhibitory effect of capsaicin but not that of piperine. Piperine inhibited the vagally mediated contractions in esophagi of adult mice neonatally injected with capsaicin, while capsaicin failed to do so. Desensitization of TRPV1 in the mouse esophagus by in vitro pretreatment with capsaicin failed to affect the inhibitory effect of piperine, whereas the piperine effect was cross-desensitized by capsaicin pretreatment in rat and hamster esophagi. Additionally, a tachykinin NK(1) receptor antagonist, L-732,138 (1 microM), as well as a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME 200 microM), blocked the inhibitory effect of capsaicin but not that of piperine. Taken together, the results suggest that piperine inhibits the vagally mediated striated muscle contraction in the mouse esophagus through its action on a TRPV1-dependent pathway as well as a TRPV1-independent site.
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PMID:Involvement of TRPV1-dependent and -independent components in the regulation of vagally induced contractions in the mouse esophagus. 1715 74

To test the hypothesis that activation of the transient receptor potential vanilloid 4 (TRPV4) channel conveys a hypotensive effect that is enhanced during salt load, male Wistar rats fed a normal-sodium (0.5%) or high-sodium (HS; 4%) diet for 3 weeks were given 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), a specific TRPV4 activator, in the presence or absence of capsazepine, a selective TRPV1 blocker, ruthenium red, a TRPV4 blocker, or TRPV4 small hairpin RNA that selectively knockdowns TRPV4. 4 alpha-PDD (1, 2.5, or 5 mg/kg IV) dose-dependently decreased mean arterial pressure (P<0.05). HS enhanced 4 alpha-PDD-induced depressor effects as well as 4 alpha-PDD-mediated release of calcitonin gene-related peptide and substance P (P<0.001). Ruthenium red markedly blunted (P<0.001), whereas capsazepine slightly attenuated (P<0.05) 4 alpha-PDD-induced depressor effects in HS and normal-sodium diet rats. Ruthenium red alone increased baseline mean arterial pressure in both HS and normal-sodium diet rats with a greater magnitude in the former (P<0.05). Western blot analysis showed that HS increased TRPV4 expression in dorsal root ganglia and mesenteric arteries (P<0.05) but not the renal cortex and medulla. Gene-silencing approach revealed that TRPV4 small hairpin RNA downregulated TRPV4 expression leading to blunted 4 alpha-PDD-induced hypotension (P<0.05). Thus, TRPV4 activation decreases blood pressure in rats given a normal-sodium diet. HS enhances TRPV4 expression in sensory nerves/mesenteric arteries and TRPV4-mediated depressor effects and calcitonin gene-related peptide/substance P release such that HS causes a greater increase in blood pressure when TRPV4 is blocked. Our data indicate that TRPV4 activation may constitute a compensatory mechanism in preventing salt-induced increases in blood pressure.
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PMID:Salt intake augments hypotensive effects of transient receptor potential vanilloid 4: functional significance and implication. 1907 88

To understand the functions of the neocortex, it is essential to characterize the properties of neurons constituting cortical circuits. Here, we focused on a distinct group of GABAergic neurons that are defined by a specific colocalization of intense labeling for both neuronal nitric oxide synthase (nNOS) and substance P (SP) receptor [neurokinin 1 (NK1) receptors]. We investigated the mechanisms of the SP actions on these neurons in visual cortical slices obtained from young glutamate decarboxylase 67-green fluorescent protein knock-in mice. Bath application of SP induced a nonselective cation current leading to depolarization that was inhibited by the NK1 antagonists in nNOS-immunopositive neurons. Ruthenium red and La(3+), transient receptor potential (TRP) channel blockers, suppressed the SP-induced current. The SP-induced current was mediated by G proteins and suppressed by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), but not by inhibitors of phosphatidylinositol-specific PLC, adenylate cyclase or Src tyrosine kinases. Ca(2+) imaging experiments under voltage clamp showed that SP induced a rise in intracellular Ca(2+) that was abolished by removal of extracellular Ca(2+) but not by depletion of intracellular Ca(2+) stores. These results suggest that SP regulates nNOS neurons by activating TRP-like Ca(2+)-permeable nonselective cation channels through a PC-PLC-dependent signaling pathway.
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PMID:Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex. 2531 39


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