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)

1. We previously demonstrated that a balance of Ca2+-activated Cl- current (ICl(Ca)) and K+ current activity sets the resting membrane potential of opossum lower esophageal sphincter (LES) circular smooth muscle at approximately -41 mV, which leads to continuous spike-like action potentials and the generation of basal tone. Ionic mechanisms underlying this basal ICl(Ca) activity and its nitrergic regulation remain unclear. Recent studies suggest that spontaneous Ca2+ release from sarcoplasmic reticulum (SR) and myosin light chain kinase (MLCK) play important roles. The current study investigated this possibility. Conventional intracellular recordings were performed on circular smooth muscle of opossum LES. Nerve responses were evoked by electrical square wave pulses of 0.5 ms duration at 20 Hz. 2. In the presence of nifedipine (1 microm), substance P (1 microm), atropine (3 microm) and guanethidine (3 microm), intracellular recordings demonstrated a resting membrane potential (MP) of -38.1+/-0.7 mV (n=25) with spontaneous membrane potential fluctuations (MPfs) of 1-3 mV. Four pulses of nerve stimulation induced slow inhibitory junction potentials (sIJPs) with an amplitude of 6.1+/-0.3 mV and a half-amplitude duration of 1926+/-147 ms (n=25). 3. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a specific guanylyl cyclase inhibitor, abolished sIJPs, but had no effects on MPfs. Caffeine, a ryanodine receptor agonist, hyperpolarized MP and abolished sIJPs and MPfs. Ryanodine (20 microm) inhibited the sIJP and induced biphasic effects on MP, an initial small hyperpolarization followed by a large depolarization. sIJPs and MPfs were also inhibited by cyclopiazonic acid, an SR Ca2+ ATPase inhibitor. Specific ICl(Ca) and MLCK inhibitors hyperpolarized the MP and inhibited MPfs and sIJPs. 4. These data suggest that (1). spontaneous release of Ca2+ from the SR activates ICl(Ca), which in turn contributes to resting membrane potential; (2). MLCK is involved in activation of ICl(Ca); (3). inhibition of ICl(Ca) is likely to underlie sIJPs induced by nitrergic innervation.
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PMID:Role of sarcoplasmic reticulum in control of membrane potential and nitrergic response in opossum lower esophageal sphincter. 1453 Feb 11

This investigation concentrates on the change in Ca(2+) concentration ([Ca(2+)]) caused by ryanodine in U373 MG cells. This cell type from a human astrocytoma is a unique cellular model because it only expresses the type 3 ryanodine receptor (RyR3), which is generally the least abundant isoform. In the presence of physiological [Ca(2+)] in the extracellular medium, U373 MG cells are caffeine-insensitive, even after forskolin treatment, and ryanodine-sensitive only when an unusually high concentration (30 microM) is applied. Xestospongin C behaves like thapsigargin and therefore cannot be used as a selective antagonist of inositol 1,4,5-trisphosphate receptors (InsP(3)Rs). After ryanodine challenge, addition of an analog of Substance P (SP), which should deplete InsP(3)-sensitive stores, has no effect on [Ca(2+)](i). After thapsigargin treatment, which unmasks the calcium leak from intracellular stores, neither ryanodine nor SP change [Ca(2+)](i), suggesting that thapsigargin completely depletes the ryanodine-sensitive and the InsP(3)-sensitive stores of U373 MG cells. Finally, in experiments monitoring the [Ca(2+)] in intracellular stores, InsP(3) stimulation of permeabilized cells causes a decrease in [Ca(2+)] that is not affected by subsequent ryanodine treatment. Our results support the conclusion that U373 MG cells express both InsP(3)Rs and RyRs that can individually or in combination mobilize only one functional Ca(2+) pool.
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PMID:Inositol 1,4,5-trisphosphate and ryanodine receptors mobilize calcium from a common functional pool in human U373 MG cells. 1545 20

Neuropeptide tachykinins, present within sensory nerves, have been implicated as neurotransmitters involved in nonadrenergic and noncholinergic airway muscle contraction. The signal transduction pathways of tachykinins on muscle contraction and Ca2+ mobilization were investigated in swine trachea. Tachykinins, substance P (SP) and neurokinin A (NKA), concentration (1 nM to 1 microM)-dependently induced contractile responses with removal of epithelium, whereas neurokinin B (NKB) did not alter the muscle tension. The SP- and NKA-evoked muscle contractions were inhibited by NK1-R antagonist L732138, but not by either NK2-R antagonist MDL29913 or NK3-R antagonist SB218795. Consistently, SP-elicited increase in [Ca2+]i was abolished by NK1-R antagonist, neither by NK2-R nor NK3-R antagonists. The SP-induced muscular responses were significantly inhibited by L-type Ca2+ channel blocker verapamil and withdrawal of external Ca2+. Caffeine (10 mM) or ryanodine (50 microM) also partly suppressed the SP-induced muscle responses. Inhibition of inositol 1,4,5-trisphosphate (InsP3) receptor with 2-APB (75 microM) potently attenuated SP-evoked Ca2+ mobilization and muscle contraction, which was further inhibited by 2-APB under Ca2+-free external solution, but not completely. Unexpectedly, simultaneous blockade of InsP3 receptor and ryanodine receptor (RyR) by 2-APB and ryanodine enhanced SP-evoked muscle contraction and Ca2+ mobilization. This potentiation was virtually abolished by removal of external Ca2+, suggesting native Ca2+ channels may contribute to this phenomenon. These results demonstrate that tachykinins produce a potent muscle contraction associated with Ca2+ mobilization via tachykinin NK1- R-dependent activation of multiple signal transduction pathways involving Ca2+ influx and release of Ca2+ from InsP3- and ryanodine-sensitive Ca2+ stores. Blockade of both InsP3 receptor and RyR enhances the Ca2+ influx through native Ca2+ channels in plasma membrane, which is crucial to Ca2+ signaling in response to NK1 receptor activation.
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PMID:Involvement of Ca2+ signaling in tachykinin-mediated contractile responses in swine trachea. 1597 Oct 6

Purinergic receptors play key signaling roles in neuropathic pain in the orofacial region, which is innervated by trigeminal ganglion (TG) neurons. The neuropathology of purinergic P2Y12 receptors is well characterized in glia; however, their physiological role in TG neurons remains to be fully elucidated. The present study investigated the expression and function of P2Y12 receptors in rat TG neurons. P2Y12 receptor immunoreactivity was intense in the soma, dendrites, and axons, and colocalized with a pan-neuronal marker, neurofilament H, isolectin B4, and substance P. In the presence of extracellular Ca(2+), 2-methylthio-ADP (an agonist of P2Y1, 12, 13 receptors) transiently increased intracellular free Ca(2+) concentrations ([Ca(2+)]i), an effect that was abolished by P2Y12 receptor antagonists. In the absence of extracellular Ca(2+), ryanodine receptor/channel inhibitors diminished the 2-methylthio-ADP-induced increases in [Ca(2+)]i. A sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor gradually increased [Ca(2+)]i, and after a plateau, application of 2-MeS-ADP induced a rapid and transient, but additive increase in [Ca(2+)]i. An adenylate cyclase inhibitor transiently increased [Ca(2+)]i, while a phosphodiesterase inhibitor prevented the 2-methylthio-ADP-induced increase in [Ca(2+)]i. Our study shows that P2Y12 receptors are expressed in TG neurons, and act via a cAMP-dependent pathway to release intracellular Ca(2+) from ryanodine-sensitive Ca(2+) stores.
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PMID:Expression and function of purinergic P2Y12 receptors in rat trigeminal ganglion neurons. 2598 95