Home About us Contact
|
Home About us Contact | ||
|
|
||
Transient Stimulation (transient + stimulation)
Selected AbstractsTrafficking of neurokinin receptors: regulation, mechanism and functionEXPERIMENTAL DERMATOLOGY, Issue 9 2004N. Bunnett Cellular responses to agonists of G-protein-coupled receptors (GPCRs) depend in large part on the trafficking of receptors between the plasma membrane and intracellular locations. Receptor activation usually triggers rapid endocytosis of receptors, which either recycle to the cell surface or are targeted for degradation, depending on the receptor in question and the nature of the stimulation. Activation of neurokinin receptors (NKRs) induces membrane translocation of G-protein receptor kinases, which phosphorylate the receptors and ,-arrestins, which interact with phosphorylated receptors. ,-arrestins: 1) uncouple receptors from G-proteins to mediate desensitization; 2) are adaptors for clathrin and AP-2 and mediate clathrin and dynamin-dependent endocytosis of receptors; and 3) interact with components of the MAP kinase pathway such as src, and thereby determine the subcellular location and function of activated MAP kinases. The fate of endocytosed NKRs depends on the receptor and the nature of the stimulus. Transient stimulation with low concentrations of SP (1 nm, 10 min) induces rapid recycling of the NK1R from superficially located endosomes by a mechanism that is mediated by rab4a and rab11a. Higher concentrations of SP (10 nm) induce rab5a-dependent trafficking of the NK1R to perinuclear sorting endosomes and a gradual recycling to the plasma membrane. Continuous stimulation with high concentrations of SP (100 nm, 180 min) induces NK1R ubiquitination and trafficking for degradation. The fate of endocytosed receptors also depends on their interaction with ,-arrestins. The NK1R forms stable high-affinity interactions with both ,-arrestins 1 and 2 at the plasma membrane and in endosomes, whereas the NK3R interacts transiently only with ,-arrestin 2 at the cell surface. The nature of these interactions is specified by domains in the intracellular loop 3 and the carboxyl terminus and determine the rate of recycling and resensitization of these receptors. [source] Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N -formyl peptide receptorsGLIA, Issue 13 2008Tursonjan Tokay Abstract Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that ,-amyloid peptide (A,) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of A, in cultured rat astrocytes. A,25,35 and the N -formyl peptide receptor (FPR) agonist N -formyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC50 value of ,2 ,M. The stimulatory effects of A,25,35 and the FPR agonists fMLF and N -formyl-Met-Met-Met (fMMM) on endozepine release were abrogated by the FPR antagonist N - t -Boc-Phe-Leu-Phe-Leu-Phe. In contrast, A,25,35 increased DBI mRNA expression through a FPR-independent mechanism. A,25,35 induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of A,25,35 on endozepine release was blocked by the adenylyl cyclase inhibitor somatostatin, the protein kinase A (PKA) inhibitor H89, the phospholipase C inhibitor U73122, the protein kinase C (PKC) inhibitor chelerythrine and the ATP binding cassette transporter blocker glyburide. Taken together, these data demonstrate for the first time that A,25,35 stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC. © 2008 Wiley-Liss, Inc. [source] Safety of pyrethroid-treated mosquito netsMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2000M. Zaim Summary The use of insecticide treated nets (ITNs) for personal protection against malaria vector Anopheles mosquitoes (Diptera: Culicidae) has become popular during the past decade. With the precautions outlined in this paper, field use of pyrethroids , at concentrations recommended for treatment of mosquito nets , poses little or no hazard to people treating the nets or to users of the treated nets. With frequent exposure to low concentrations of pyrethroids, the risk of toxicity of any kind is remote. Pyrethroids entering the systemic circulation are rapidly metabolized to much less toxic metabolites. Toxicologically, pyrethroids have a useful characteristic , the production of skin paraesthesia , which gives an early indication of exposure. This reversible symptom of exposure is due to transient stimulation of peripheral sensory nerves and not a toxic effect. In the retail market, for home use, the provision of proper packaging and labelling, with clear instructions on safe and effective use of the product are most important. Because many domestic users of pyrethroid ,home treatment kits' for ITNs may not be fully literate, it is essential that ,instructions for use' should be portrayed via pictograms with supporting text in appropriate local language(s). [source] cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2007Sunita Warrier Many different receptors can stimulate cAMP synthesis in the heart, but not all elicit the same functional responses. For example, it has been recognized for some time that prostaglandins such as PGE1 increase cAMP production and activate PKA, but they do not elicit responses like those produced by ,-adrenergic receptor (,AR) agonists such as isoproterenol (isoprenaline), even though both stimulate the same signalling pathway. In the present study, we confirm that isoproterenol, but not PGE1, is able to produce cAMP-dependent stimulation of the L-type Ca2+ current in guinea pig ventricular myocytes. This is despite finding evidence that these cells express EP4 prostaglandin receptors, which are known to activate Gs -dependent signalling pathways. Using fluorescence resonance energy transfer-based biosensors that are either freely diffusible or bound to A kinase anchoring proteins, we demonstrate that the difference is due to the ability of isoproterenol to stimulate cAMP production in cytosolic and caveolar compartments of intact cardiac myocytes, while PGE1 only stimulates cAMP production in the cytosolic compartment. Unlike other receptor-mediated responses, compartmentation of PGE1 responses was not due to concurrent activation of a Gi -dependent signalling pathway or phosphodiesterase activity. Instead, compartmentation of the PGE1 response in cardiac myocytes appears to be due to transient stimulation of cAMP in a microdomain that can communicate directly with the bulk cytosolic compartment but not the caveolar compartment associated with ,AR regulation of L-type Ca2+ channel function. [source] Effects of (-)bicuculline and gamma-aminobutyric acid on the NiCl2 mediated stimulation of the ERG b-wave amplitude from the isolated superfused vertebrate retinaACTA OPHTHALMOLOGICA, Issue 2007T SCHNEIDER Purpose: NiCl2 (15 ,M) stimulates the b-wave amplitude of vertebrate retina, up to 1.5-fold through its blocking of E/R-type voltage-gated Ca2+ channels. Assuming that these channels may trigger the release of the inhibitory neurotransmitter GABA, we tested the effect of (-)bicuculline and GABA itself. Methods: We have used a superfused vertebrate retina assay, testing retina from bovine (Lüke et al., 2005: Brain Res Brain Res Protoc 16 : 27-36). The retina was separated from the underlying pigment epithelium and mounted on a mesh occupying the center of the perfusing chamber. The electroretinogram was recorded in the surrounding nutrient medium via two silver/silver-chloride electrodes on either side of the retina. The recording chamber containing a piece of retina was placed in an electrically and optically insulated air thermostat. The retina was dark-adapted and the electroretinogram was elicited at intervals of five min using a single white flash for stimulation. Results: (-)Bicuculline increased the b-wave amplitude to a similar extent as observed in parallel recordings for low NiCl2 (15 ,M). The GABA effect was biphasic, and let to a transient stimulation after NiCl2 application. Those retina segments which did not respond to NiCl2 (15 ,M), also could not be stimulated by bicuculline and vice versa. Conclusions: The stimulatory effect of NiCl2 on the ERG b-wave amplitude is mediated by a NiCl2-sensitive, probably Cav2.3 / voltage-gated Ca2+-channel triggered GABA-release, and GABA itself may act on at least two different receptors. [source] | |||||||||||||