scholarly journals TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Tunyu Jian ◽  
Niuniu Yang ◽  
Yan Yang ◽  
Chan Zhu ◽  
Xiaolin Yuan ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Underlying Mechanism ◽  
Receptor Activation ◽  
Ruthenium Red ◽  
Drg Neurons ◽  
Histamine H4 Receptor ◽  
Signaling Mechanism ◽  
Downstream Signaling ◽  
Intracellular Ca ◽  
H4 Receptor

Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)—a histamine H4 receptor special agonist under cutaneous injection—obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3–50 μM) could also induce a dose-dependent increase in intracellular Ca2+(Ca2+i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca2+responses. In addition, immepip-inducedCa2+iincrease could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons’ responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.

scholarly journals Diversification of Disease Resistance Receptors by Integrated Domain Fusions in Wheat and its Progenitors

2019 ◽  
Author(s):  
Ethan J. Andersen ◽  
Madhav P. Nepal
Keyword(s):  
Intracellular Signaling ◽  
Defense Responses ◽  
Receptor Activation ◽  
Alternative Transcripts ◽  
Downstream Signaling ◽  
Id Genes ◽  
Integrated Domains ◽  
Effector Recognition ◽  
Encoding Genes ◽  
Signaling Components

ABSTRACTPathogenic effectors inhibit plant resistance responses by interfering with intracellular signaling mechanisms. Plant Nucleotide-binding, Leucine-rich repeat Receptors (NLRs) have evolved highly variable effector-recognition sites to detect these effectors. While many NLRs utilize variable Leucine-Rich Repeats (LRRs) to bind to effectors, some have gained Integrated Domains (IDs) necessary for receptor activation or downstream signaling. While a few studies have identified IDs within NLRs, the homology and regulation of these genes have yet to be elucidated. We identified a diverse set of wheat NLR-ID fusion proteins as candidates for NLR functional diversification through ID effector recognition or signal transduction. NLR-ID diversity corresponds directly with the various signaling components essential to defense responses, expanding the potential functions for immune receptors and removing the need for intermediate signaling factors that are often targeted by effectors. ID homologs (>80% similarity) in other grasses indicate that these domains originated as functional, non-NLR-encoding genes and were incorporated into NLR-encoding genes through duplication. Multiple NLR-ID genes encode experimentally verified alternative transcripts that include or exclude IDs. This indicates that plants employ alternative splicing to regulate IDs, possibly using them as baits, decoys, and functional signaling components. Future studies should aim to elucidate differential expression of NLR-ID alternative transcripts.

scholarly journals Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling

2015 ◽  
Vol 112 (38) ◽  
pp. 11876-11880 ◽  
Author(s):  
Askar M. Akimzhanov ◽  
Darren Boehning
Keyword(s):  
Tyrosine Kinase ◽  
Protein Function ◽  
Intracellular Signaling ◽  
Signaling Mechanism ◽  
Fas Receptor ◽  
Downstream Signaling ◽  
Fatty Acid Chain ◽  
Protein Palmitoylation ◽  
Thioester Bond ◽  
Fas Signaling

Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck. Lck palmitoylation kinetics are consistent with the activation of downstream signaling proteins, such as Zap70 and PLC-γ1. Inhibiting Lck palmitoylation not only disrupts proximal Fas signaling events, but also renders cells resistant to Fas-mediated apoptosis. Knockdown of the palmitoyl acyl transferase DHHC21 eliminates activation of Lck and downstream signaling after Fas receptor stimulation. Our findings demonstrate highly dynamic Lck palmitoylation kinetics that are essential for signaling downstream of the Fas receptor.

In Silico Characterization of Ligand Binding Modes in the Human Histamine H4 Receptor and their Impact on Receptor Activation

ChemBioChem ◽  
2010 ◽  
Vol 11 (13) ◽  
pp. 1850-1855 ◽  
Author(s):  
Tim Werner ◽  
Kerstin Sander ◽  
Yusuf Tanrikulu ◽  
Tim Kottke ◽  
Ewgenij Proschak ◽  
...  
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Receptor Activation ◽  
Binding Modes ◽  
Histamine H4 Receptor ◽  
H4 Receptor ◽  
In Silico Characterization ◽  
Human Histamine

Role of TRPV1 and intracellular Ca2+ in excitation of cardiac sensory neurons by bradykinin

2007 ◽  
Vol 293 (1) ◽  
pp. R276-R283 ◽  
Author(s):  
Zi-Zhen Wu ◽  
Hui-Lin Pan
Keyword(s):  
Sensory Neurons ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Drg Neurons ◽  
Excitatory Effect ◽  
Trpv1 Channels ◽  
Intracellular Ca ◽  
Spinal Afferents ◽  
12 Lipoxygenase

Bradykinin is an important mediator produced during myocardial ischemia and infarction that can activate and/or sensitize cardiac spinal (sympathetic) sensory neurons to trigger chest pain. Because a long-onset latency is associated with the bradykinin effect on cardiac spinal afferents, a cascade of intracellular signaling events is likely involved in the action of bradykinin on cardiac nociceptors. In this study, we determined the signal transduction mechanisms involved in bradykinin stimulation of cardiac nociceptors. Cardiac dorsal root ganglion (DRG) neurons in rats were labeled by intracardiac injection of a fluorescent tracer, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine percholate (DiI). Whole cell current-clamp recordings were performed in acutely isolated DRG neurons. In DiI-labeled DRG neurons, 1 μM bradykinin significantly increased the firing frequency and lowered the membrane potential. Iodoresiniferatoxin, a highly specific transient receptor potential vanilloid type 1 (TRPV1) antagonist, significantly reduced the excitatory effect of bradykinin. Furthermore, the stimulating effect of bradykinin on DiI-labeled DRG neurons was significantly attenuated by baicalein (a selective inhibitor of 12-lipoxygenase) or 2-aminoethyl diphenylborinate [an inositol 1,4,5-trisphosphate (IP3) antagonist]. In addition, the effect of bradykinin on cardiac DRG neurons was abolished after the neurons were treated with BAPTA-AM or thapsigargin (to deplete intracellular Ca2+ stores) but not in the Ca2+-free extracellular solution. Collectively, these findings provide new evidence that 12-lipoxygenase products, IP3, and TRPV1 channels contribute importantly to excitation of cardiac nociceptors by bradykinin. Activation of TRPV1 and the increase in the intracellular Ca2+ are critically involved in activation/sensitization of cardiac nociceptors by bradykinin.

Histamine H4 receptor activation alleviates neuropathic pain through differential regulation of ERK, JNK, and P38 MAPK phosphorylation

Pain ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 2492-2504 ◽  
Author(s):  
Maria D. Sanna ◽  
Holger Stark ◽  
Laura Lucarini ◽  
Carla Ghelardini ◽  
Emanuela Masini ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
P38 Mapk ◽  
Receptor Activation ◽  
Differential Regulation ◽  
Histamine H4 Receptor ◽  
Mapk Phosphorylation ◽  
H4 Receptor

Role of the second and third extracellular loops of the histamine H4 receptor in receptor activation

2011 ◽  
Vol 384 (3) ◽  
pp. 301-317 ◽  
Author(s):  
Irena Brunskole ◽  
Andrea Strasser ◽  
Roland Seifert ◽  
Armin Buschauer
Keyword(s):  
Receptor Activation ◽  
Histamine H4 Receptor ◽  
Extracellular Loops ◽  
H4 Receptor

ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms

2005 ◽  
Vol 288 (1) ◽  
pp. C204-C213 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Intracellular Signaling ◽  
Anion Channel ◽  
Cell Swelling ◽  
Organic Osmolytes ◽  
Signaling Mechanism ◽  
Pharmacological Agents ◽  
Organic Osmolyte ◽  
Primary Astrocyte ◽  
Intracellular Ca ◽  
Rat Astrocytes

Ubiquitously expressed volume-regulated anion channels (VRACs) are activated in response to cell swelling but may also show limited activity in nonswollen cells. VRACs are permeable to inorganic anions and small organic osmolytes, including the amino acids aspartate, glutamate, and taurine. Several recent reports have demonstrated that neurotransmitters or hormones, such as ATP and vasopressin, induce or strongly potentiate astrocytic whole cell Cl− currents and amino acid release, which are inhibited by VRAC blockers. In the present study, we explored the intracellular signaling mechanisms mediating the effects of ATP on d-[3H]aspartate release via the putative VRAC pathway in rat primary astrocyte cultures. Cells were exposed to moderate (5%) or substantial (30%) reductions in medium osmolarity. ATP strongly potentiated d-[3H]aspartate release in both moderately swollen and substantially swollen cells. These ATP effects were blocked (≥80% inhibition) by intracellular Ca2+ chelation with BAPTA-AM, calmodulin inhibitors, or a combination of the inhibitors of protein kinase C (PKC) and calmodulin-dependent kinase II (CaMK II). In contrast, control d-[3H]aspartate release activated by the substantial hyposmotic swelling showed little (≤25% inhibition) sensitivity to the same pharmacological agents. These data indicate that ATP regulates VRAC activity via two separate Ca2+-sensitive signaling cascades involving PKC and CaMK II and that cell swelling per se activates VRACs via a separate Ca2+/calmodulin-independent signaling mechanism. Ca2+-dependent organic osmolyte release via VRACs may contribute to the physiological functions of these channels in the brain, including astrocyte-to-neuron intercellular communication.

Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas

2007 ◽  
Vol 292 (1) ◽  
pp. G349-G357 ◽  
Author(s):  
María E. Sabbatini ◽  
Marcelo S. Vatta ◽  
Carlos A. Davio ◽  
Liliana G. Bianciotti
Keyword(s):  
Intracellular Signaling ◽  
Atrial Natriuretic Factor ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Signaling Mechanism ◽  
Pancreatic Acini ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

We previously reported that atrial natriuretic factor (ANF) stimulates pancreatic secretion through NPR-C receptors coupled to PLC and potentiates secretin response without affecting cAMP levels. In the present study we sought to establish the intracellular signaling mechanism underlying the interaction between both peptides. In isolated pancreatic acini 100 nM ANF abolished cAMP accumulation evoked by any dose of secretin. Lower doses of ANF (1 fM, 1 pM, 1 and 10 nM) dose dependently reduced EC50 secretin-evoked cAMP. Although ANF failed to affect cAMP stimulated by amthamine (selective H2 agonist) or isoproterenol (β-adrenergic agonist), it abolished VIP-induced cAMP formation. ANF inhibitory effect was prevented by U-73122 (PLC inhibitor) and GF-109203X (PKC inhibitor) but unaltered by PKG and nitric oxide synthase inhibition, supporting that the PLC/PKC pathway mediated the effect. ANF response was mimicked by cANP (4–23 amide) and abolished by pertussis toxin, strongly supporting NPR-C receptor activation. In vivo studies showed that ANF at 0.5 μg·kg−1·h−1 enhanced secretion stimulated by 1 U·kg−1·h−1 secretin but at 1 and 2 μg·kg−1·h−1 it abolished secretin response. However, ANF at such doses failed to modify the secretion evoked by carbachol or CCK. Present results show that ANF negatively modulated secretin secretory response and intracellular signaling through the activation of NPR-C receptors coupled to the PLC/PKC pathway. Furthermore, the finding that ANF also inhibited VIP-evoked cAMP supports a selective modulation of class II G-protein coupled receptors by ANF. Present findings suggest that ANF may play a protective role by reducing secretin response to avoid overstimulation.

Sign in / Sign up

Export Citation Format

Share Document