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Selective Action (selective + action)
Selected AbstractsKv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminalsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Ruth E. Brooke Abstract Voltage-gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light- and electron-microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end-plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05,0.5 mm), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large-conductance calcium-activated potassium channel blockers iberiotoxin (25,150 nm) and Penitrem A (100 nm), suggesting a selective action on Kv3 subunits. Consistent with this, 15-µm 4-aminopyridine, which blocks Kv3 but not large-conductance calcium-activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood-depressing substance-I, a toxin selective for Kv3.4 subunits, had no effect at 0.05,1 µm. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ. [source] GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004Mario Engelmann Abstract Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA -receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion. [source] 5-HT inhibits N-type but not L-type Ca2+ channels via 5-HT1A receptors in lamprey spinal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Russell H. Hill Abstract 5-HT is a potent modulator of locomotor activity in vertebrates. In the lamprey, 5-HT dramatically slows fictive swimming. At the neuronal level it reduces the postspike slow afterhyperpolarization (sAHP), which is due to apamin-sensitive Ca2+ -dependent K+ channels (KCa). Indirect evidence in early experiments suggested that the sAHP reduction results from a direct action of 5-HT on KCa channels rather than an effect on the Ca2+ entry during the action potential [Wallén et al., (1989) J. Neurophysiol., 61, 759,768]. In view of the characterization of different subtypes of Ca2+ channels with very different properties, we now reinvestigate if there is a selective action of 5-HT on a Ca2+ channel subtype in dissociated spinal neurons in culture. 5-HT reduced Ca2+ currents from high voltage activated channels. N-type, but not L-type, Ca2+ channel blockers abolished this 5-HT-induced reduction. It was also confirmed that 5-HT depresses Ca2+ currents in neurons, including motoneurons, in the intact spinal cord. 8-OH-DPAT, a 5-HT1A receptor agonist, also inhibited Ca2+ currents in dissociated neurons. After incubation in pertussis toxin, to block Gi/o proteins, 5-HT did not reduce Ca2+ currents, further indicating that the effect is caused by an activation of 5-HT1A receptors. As N-type, but not L-type, Ca2+ channels are known to mediate the activation of KCa channels and presynaptic transmitter release at lamprey synapses, the effects of 5-HT reported here can contribute to a reduction in both actions. [source] Late lethal hepatitis B virus reactivation after rituximab treatment of low-grade cutaneous B-cell lymphomaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006G. Perceau Summary The chimeric anti-CD20 monoclonal antibody, rituximab, is a promising treatment for cutaneous B-cell lymphomas. Classically used in combination with a multiagent-chemotherapy regimen, it can sometimes give excellent results alone. Because of its selective action on B lymphocytes, it is considered a moderate immunosuppressant in terms of infection. We describe a woman with relapsed cutaneous follicular centre B-cell lymphoma and secondary lymph-node involvement treated with rituximab alone, which induced a complete remission. One year later, she experienced a fatal hepatitis B virus (HBV) reactivation. Several such HBV reactivations were reported after combined rituximab and multiagent chemotherapy for B-cell lymphomas. This is the first case of HBV reactivation occurring during the year following rituximab monotherapy in the absence of any other immunosuppressive factor. [source] Casearin X, Its Degradation Product and Other Clerodane Diterpenes from Leaves of Casearia sylvestris: Evaluation of Cytotoxicity against Normal and Tumor Human CellsCHEMISTRY & BIODIVERSITY, Issue 1 2010André Gonzaga, Santos Abstract An EtOH extract of the leaves of Casearia sylvestris afforded new clerodane diterpene, casearin X, together with the known compounds casearins B, D, L, and O, and caseargrewiin F. Casearin X degraded to the corresponding dialdehyde when stored in CDCl3. The diterpenes isolated were cytotoxic to human cancer cell lines, with caseargrewiin F being the most active and the new clerodane, casearin X, the second active compound with IC50 values comparable to the positive control doxorubicin. All isolated diterpenes showed lower activities against normal human cells than against cancer cell lines, which might indicate a possible selective action on cancer cells. Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity. [source] Dopamine, Morphine, and Nitric Oxide: An Evolutionary Signaling TriadCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 3 2010George B. Stefano Morphine biosynthesis in relatively simple and complex integrated animal systems has been demonstrated. Key enzymes in the biosynthetic pathway have also been identified, that is, CYP2D6 and COMT. Endogenous morphine appears to exert highly selective actions via novel mu opiate receptor subtypes, that is, mu3,-4, which are coupled to constitutive nitric oxide release, exerting general yet specific down regulatory actions in various animal tissues. The pivotal role of dopamine as a chemical intermediate in the morphine biosynthetic pathway in plants establishes a functional basis for its expansion into an essential role as the progenitor catecholamine signaling molecule underlying neural and neuroendocrine transmission across diverse animal phyla. In invertebrate neural systems, dopamine serves as the preeminent catecholamine signaling molecule, with the emergence and limited utilization of norepinephrine in newly defined adaptational chemical circuits required by a rapidly expanding set of physiological demands, that is, motor and motivational networks. In vertebrates epinephrine, emerges as the major end of the catecholamine synthetic pathway consistent with a newly incorporated regulatory modification. Given the striking similarities between the enzymatic steps in the morphine biosynthetic pathway and those driving the evolutionary adaptation of catecholamine chemical species to accommodate an expansion of interactive but distinct signaling systems, it is our overall contention that the evolutionary emergence of catecholamine systems required conservation and selective "retrofit" of specific enzyme activities, that is, COMT, drawn from cellular morphine expression. Our compelling hypothesis promises to initiate the reexamination of clinical studies, adding new information and treatment modalities in biomedicine. [source] | ||||||||||