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 plasma membrane calcium ATPase pump (PMCA) is one of two major mechanisms known to be involved in extruding calcium from cells. The monoclonal antibody 5F10 was used to examine the distribution of PMCA in chick Edinger-Westphal neurons, a population of cholinergic preganglionic neurons whose cells bodies reside in the Edinger-Westphal nucleus in the brainstem and whose axons form synaptic terminals on parasympathetic neurons in the ciliary ganglion. Definitive PMCA immunoreactivity was undetectable in Edinger-Westphal cell bodies in the brainstem. In contrast, immunoreactivity for PMCA was robust in ciliary ganglia and resembled patterns of immunoreactivity for the synaptic vesicle antigen SV-2, suggesting that PMCA is expressed in Edinger-Westphal synaptic terminals. Moreover, PMCA immunoreactivity co-localized with immunoreactivity for enkephalin and substance P, two neuropeptides known to be expressed in Edinger-Westphal synaptic terminals. Fine structure studies revealed that PMCA immunoreactivity is associated with synaptic vesicles rather than the plasma membrane in Edinger-Westphal terminals. In immunodot assays, synaptic vesicles purified from Torpedo electric organ are also immunoreactive for PMCA as well as SV-2. Torpedo vesicles are negative for the sarcoplasmic/ endoplasmic reticulum ATPase, suggesting that the observed PMCA immunoreactivity is not associated with smooth endoplasmic reticulum. Immunoblot analysis confirmed that 5F10 recognizes a protein with the correct molecular mass for PMCA in tissue homogenates of chick cerebellum, chick ciliary ganglia, and Torpedo synaptic vesicles. These findings describe a previously unrecognized location for PMCA in the membranes of cholinergic synaptic vesicles. Relevance to previous data and possible functions are discussed.
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PMID:Plasma membrane calcium ATPase in synaptic terminals of chick Edinger-Westphal neurons. 889 25

Signaling pathways activated by the tachykinin substance P (SP) were investigated in pig coronary artery endothelial cells (PCAECs). Single cells were obtained after enzymatic digestion of coronary arteries. Intracellular Ca2+ ([Ca2+]i) was measured from fura-2 fluorescence while membrane potential or ionic current was measured using patch-clamp techniques. In physiological saline solution, SP induced hyperpolarizations or outward currents which coincided with biphasic [Ca2+]i increases representing store release of Ca2+ and Ca2+ influx. Single channel recording protocols showed that both sources of Ca2+ activated a small conductance K+ channel, resulting in cell hyperpolarization. When outward currents were blocked by d-tubocurare, Cs+, or BAPTA, an inward current was unmasked. Ion substitution protocols showed that the SP-induced inward current was (1) carried by a mixture of Ca2+ and Na+, (2) blocked by La3+, and (3) inactivated by high extracellular [Ca2+]. Tyrosine kinase inhibitors also blocked the inward current. The same current was activated by bath application of BHQ, an inhibitor of the endoplasmic reticulum Ca2+ ATPase, or by cell dialysis with IP3. These results suggest that the plateau phase of the agonist-activated [Ca2+]i increase in PCAECs reflects Ca2+ entry through a depletion-activated Ca2+ channel. The characteristics of this channel are compared to those of Ca2+ channels found in other nonexcitable cells.
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PMID:Calcium-release-activated calcium influx in endothelium. 922

The regulation of Ca2+ mobilization in the human submandibular duct cell line A253 was investigated by monitoring cytosolic free Ca2+ concentrations ([Ca2+]i) using the Ca(2+)-sensitive fluorescent indicator fura-2 and by measuring inositol 1,4,5-triphosphate (IP3) formation. An increase in [Ca2+]i was elicited by ATP, isoproterenol (IPR), or vasoactive intestinal polypeptide (VIP), but not by acetylcholine, norepinephrine, or substance P, suggesting that Ca2+ mobilization is regulated by P2-purinergic, beta 2-adrenergic, and VIP receptors. 1,4,5-IP3 formation was significantly increased by ATP but not by the other agonists. Exposure of the cells to a membrane permeable cAMP analog, dibutyryl-cAMP, or to the adenylate cyclase activator forskolin induced a smaller increase in [Ca2+]i, indicating that the IPR-induced Ca2+ release is not mediated by cyclic AMP. Inhibition of the endoplasmic Ca(2+)-ATPase with thapsigargin (TG) in Ca(2+)-free medium induced a 207% increase in [Ca2+]i, and a subsequent exposure to ATP caused a further increase in [Ca2+]i of 104%. Similarly, TG exposure after ATP induced a further Ca2+ release, suggesting that the TG-sensitive store and the IP3-sensitive store do not overlap. Similar results were observed by sequential exposure to TG and IPR or to ATP and IPR. Ca2+ influx across the plasma membrane was enhanced after ATP or TG, but not after IPR. Our findings show a unique pattern of Ca2+ mobilization in the A253 cell line: (i) Ca2+ mobilization is regulated by P2-purinergic, beta 2-adrenergic, and VIP receptors; (ii) Ca2+ release is mediated by 1,4,5-IP3 and probably by an unknown mediator; (iii) TG, P2-, and beta 2-agonists discharge separate Ca2+ stores; and (iv) ATP and TG, but not IPR, regulate Ca2+ influx.
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PMID:Characterization of Ca2+ mobilization in the human submandibular duct cell line A253. 931 20

1. Ouabain, an inhibitor of Na+/K+ ATPase induces the release of acetylcholine from central and myenteric cholinergic neurones principally due to partial depolarization of the cell membrane. The effect of ouabain has been examined on neurogenic contractions in the guinea-pig ileum arising from either electrical field stimulation or from naloxone in morphine-exposed preparations. 2. Guinea-pig isolated ileum preparations were stimulated transmurally (0.1 Hz, 0.3 ms, 200 mA) to elicit contractions of the myenteric plexus-longitudinal smooth muscle. 3. Incubation with morphine (0.3 microM, 60 min) was followed by naloxone (1 microM) which produced withdrawal contractions in 16/26 preparations (median of 10.7 [2.2-40.0]% of a maximal contracture to KCl (60 mM)). 4. In parallel experiments, ouabain (1 microM) was added to the tissue before exposure to morphine (0.3 microM, 60 min). Naloxone (1 microM) subsequently displayed a withdrawal contraction in all 26/26 tissues (57.9 [30.5-151.7]% of a maximal contracture to KCl (60 mM). 5. Ouabain neither affected the concentration-dependent contractions of guinea-pig ileum produced by carbachol nor the inhibition of electrically-evoked contraction produced by morphine (0.3 microM). 6. The muscarinic antagonist atropine (0.1 microM) antagonized control naloxone withdrawal responses. The atropine resistant component, evident in ouabain-treated tissues, was blocked by SR140333((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenyla cetyl)piperidin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2. 2]-octane, chloride), a substance P antagonist. 7. Clonidine (alpha2-adrenoceptor agonist) inhibited electrically-evoked contractions. Exposure to the alpha2-adrenoceptor antagonist RX811059 (2-(2-ethoxy-1,4-benzodioxan-2-yl)-2-imidazoline), resulted in a contracture which was not significantly enhanced by ouabain (1 microM). 8. Ouabain selectively potentiates the naloxone-induced withdrawal contraction following acute exposure to morphine the major components of which are mediated by both acetylcholine and substance P.
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PMID:Selective potentiation by ouabain of naloxone-induced withdrawal contractions of isolated guinea-pig ileum following acute exposure to morphine. 969 76

Stretching the renal pelvic wall increases ipsilateral afferent renal nerve activity (ARNA). This response is enhanced by inhibiting Na+-K+-ATPase with ouabain, suggesting a modulatory role for intracellular Na+ in the activation of mechanosensitive neurons. The messenger RNA for alpha-, beta-, and gamma-subunits of epithelial Na+ channels (ENaC) is found in collecting duct cells. Because ENaC subunits show homology with genes involved in mechanosensation, we examined whether ENaC mRNA could be found in the pelvic wall and whether the ARNA response to increased renal pelvic pressure was modulated by blockers of the Na+ channel. alpha-, beta-, and gamma-subunits are present in the pelvis. The messenger RNA for the beta- and gamma-subunits is readily detected by in situ hybridization throughout the uroepithelium. The ARNA response to increased renal pelvic pressure was reduced by 53 +/- 10% and 40 +/- 10% (P < 0.01) by renal pelvic perfusion with the inhibitors amiloride and benzamil, respectively. Amiloride inhibited the ouabain-induced enhancement of the ARNA response to increased renal pelvic pressure. The magnitude of this inhibition was inversely correlated with the magnitude of the amiloride-mediated blockade of the ARNA response to increased renal pelvic pressure (P < 0.001). Amiloride also reduced the ARNA response to renal pelvic administration of substance P, a mediator of the ARNA response to increased renal pelvic pressure. We conclude that the ENaC complex in the pelvic uroepithelium participates in the activation of renal pelvic mechanosensitive neurons.
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PMID:Amiloride-sensitive Na+ channels in pelvic uroepithelium involved in renal sensory receptor activation. 984 67

Sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 3 (SERCA3), an isoform of the intracellular Ca(2+) pump that has been shown to mediate endothelium-dependent relaxation of vascular smooth muscle, is also expressed in tracheal epithelium. To determine its possible role in regulation of airway mechanical function, we compared tracheal contractility in gene-targeted mice deficient in SERCA3 (SERCA3(-)) with that in wild-type tracheae. Cumulative addition of ACh elicited concentration-dependent increases in isometric force (ED(50) = 2 microM, maximum force = 8 mN/mm(2)) that were identical in SERCA3(-) and wild-type tracheae. After ACh stimulation, substance P (SP) elicited a transient relaxation (42.6 +/- 3.2%, n = 28) in both tracheae. However, the rate of relaxation was significantly (P < 0.04, n = 9) more rapid in the wild-type [half-time (t(1/2)) = 34.3 s] than in the SERCA3(-) (t(1/2) = 61.6 s) trachea. The SP relaxation was reduced by rubbing the trachea, indicative of epithelial cell involvement. This was verified using a perfused trachea preparation. SP in the outside medium had no effect, whereas SP in the perfusate bathing the epithelial side elicited a relaxation. Nitric oxide synthase inhibition (0.2 mM N(omega)-nitro-L-arginine) reduced the SP relaxation by 36.5 +/- 12.5%, whereas the SP effect was abolished by eicosanoid inhibition (10 microM indomethacin). ATP also elicited an epithelium-dependent relaxation similar to SP but with a more rapid relaxation in the SERCA3(-) trachea than in the wild-type trachea. Our results indicate that SERCA3 gene ablation does not directly affect smooth muscle, which is consistent with the distribution of the isoform, but suggest that SERCA3 plays a role in epithelial cell modulation of airway smooth muscle function.
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PMID:Ablation of the SERCA3 gene alters epithelium-dependent relaxation in mouse tracheal smooth muscle. 1044 20

In the present study, we have used a non-denaturing gel electrophoresis assay to characterize the specificity of the peptide-induced depolymerization process of the isolated recombinant C-terminal domain (C30) of the molecular chaperone BiP, in the presence of specific synthetic peptides and with the neuropeptide Substance P. In the absence of peptidic ligand, C30 self-associates readily into multiple oligomeric species. Upon peptide addition, C30 oligomers convert into dimers, then into monomers. Our data indicate that the algorithm we previously developed to predict putative BiP binding sites in any protein sequence is also a good indicator as to whether a peptide can efficiently induce depolymerization of the C-terminal peptide binding domain and stimulate the ATPase activity of the full-length protein.
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PMID:Specificity of peptide-induced depolymerization of the recombinant carboxy-terminal fragment of BiP/GRP78. 1048 74

In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identified as potassium. Potassium hyperpolarizes the smooth muscles by gating inward rectified potassium channels and by activating the sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase). Our goal was to examine whether potassium could explain the EDHF in porcine coronary arteries. On coronary strips, the inhibition of calcium-dependent potassium channels with 100 nM apamin plus 100 microM charibdotoxin inhibited the endothelium-dependent relaxations, produced by 10 nM substance P and 300 nM bradykinin and resistant to nitro-L-arginine and indomethacin. The scavenging of potassium with 2 mM Kryptofix 2.2.2 abolished the endothelium-dependent relaxations produced by the kinins and resistant to nitro-L-arginine and indomethacin. Forty microM 18alpha glycyrrethinic acid or 50 microM palmitoleic acid, both uncoupling agents, did not inhibit these kinin relaxations. Therefore, EDHF does not result from an electrotonic spreading of an endothelial hyperpolarization. Barium (0.3 nM) did not inhibit the kinin relaxations resistant to nitro-L-arginine and indomethacin. Therefore, EDHF does not result from the activation of inward rectified potassium channels. Five hundred nM ouabain abolished the endothelium-dependent relaxations resistant to nitro-L-arginine and indomethacin without inhibiting the endothelium-derived NO relaxation. The perifusion of a medium supplemented with potassium depolarized and contracted a coronary strip; however, the short application of potassium hyperpolarized the smooth muscles. These results are compatible with the concept that, in porcine coronary artery, the EDHF is potassium released by the endothelial cells and that this ion hyperpolarizes and relaxes the smooth muscles by activating the Na(+)-K(+)ATPase.
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PMID:An evaluation of potassium ions as endothelium-derived hyperpolarizing factor in porcine coronary arteries. 1105 18

Mast cells exocytotically release histamine/serotonin in response to different secretagogues. We have used substance P and compound 48/80 to study the Ca++ dependency of serotonin exocytosis from peritoneal mast cells using carbon fiber amperometric techniques. The exocytotic release pattern consists of a burst of events superimposed on a slow, transient, amperometric current baseline increase. Cellular re lease parameters (number, frequency and total charge of amperometric events) and individual event characteristics (charge integral, half width and peak amplitude) were similar for the two secretagogues used. Zero Ca++ conditions greatly reduced, without completely abolishing,cellular release parameters. Cyclopiazonic acid, an inhibitor of the endoplasmatic Ca++ ATPase, reduced the cellular exocytotic capacity and diminished the amplitude of individual exocytotic events more effectively than the 0 Ca++ condition. The cyclopiazonic acid effects occurred in the presence of external Ca++, indicating that this condition is not sufficient for maintaining full exocytotic capacity. The results confirm the importance of intracellular Ca++ for exocytotic activation. For the first time evidence is presented that the integrity of intracellular Ca++ pools determines the amplitude and frequency of individual exocytotic events. Saponin, a non-specific detergent, also induced quantal release similar to that obtained with substance P and compound 48/80. This release was not dependent on extracellular Ca++, but cyclopiazonic acid significantly reduced individual exocytotic release.
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PMID:Amperometric characterization of exocytotic events from single mast cells: dependence on external and internal Ca++ sources. 1116 57

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


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