Human recombinant interleukin-1 beta inhibits nicotinic transmission in neurons of guinea pig pelvic plexus ganglia

1995 ◽  
Vol 269 (6) ◽  
pp. G981-G987 ◽  
Author(s):  
J. Lin ◽  
J. Krier

The actions of human recombinant interleukin-1 beta (hrIL-1 beta) were tested on guinea pig pelvic plexus ganglion neurons using intracellular electrophysiological methods in vitro. hrIL-1 beta caused membrane depolarization associated with a decreased input resistance or inward currents in 54% of neurons tested. hrIL-1 beta caused a hyperpolarization associated with an increase in input resistance or outward currents in 30% of neurons tested. hrIL-1 beta-evoked responses were not altered by hexamethonium (100 microM), atropine (0.5 microM), yohimbine (0.3 microM), or naloxone (1 microM), indicating that cholinergic, alpha 2-adrenergic, or opioid receptors were not involved. Drugs that inhibit Na+, Ca2+, or K+ channels did not change hrIL-1 beta-evoked responses. Stimulation of synaptic inputs to pelvic ganglion neurons evoked nicotinic cholinergic fast excitatory postsynaptic potentials (fEPSPs). hrIL-1 beta inhibited fEPSPs in 44% of neurons tested but had no effect on acetylcholine-induced depolarizations. An IL-1 beta receptor antagonist blocked all actions of hrIL-1 beta. In summary, hrIL-1 beta has excitatory and inhibitory actions on pelvic ganglion neurons. Inhibition of fEPSPs by hrIL-1 beta may be due to presynaptic inhibition of acetylcholine release.

1991 ◽  
Vol 261 (5) ◽  
pp. R1096-R1103 ◽  
Author(s):  
M. Shibata ◽  
C. M. Blatteis

This study was undertaken to determine whether the reported different courses of the febrile responses to the cytokines interleukin-1 beta (IL-1), interferon-alpha 2 (IFN), and tumor necrosis factor-alpha (TNF) might have neuroelectrophysiological correlates. The reactions of individual thermosensitive neurons in the preoptic area (POA) were evaluated by recording their extracellular single-unit firing rates (FR) in slices of guinea pig POA perfused with artificial cerebrospinal fluid (aCSF), human recombinant IL-1 (50-500 ng), IFN (1,000-8,000 U), and TNF (400-5,000 ng) (all doses per min/ml aCSF); thermosensitivity was assessed by FR responses to changes of perfusate temperature (32-42 degrees C). Overall, these cytokines depressed the FR of warm-sensitive units and excited those of cold-sensitive units, in agreement with expectations. However, the responses of individual neurons treated with two or all three cytokines were dissimilar: 61% of the units tested reacted differentially to two or three cytokines, 32% exhibited identical responses, and 7% had no response to any cytokine. These results support the possibility that IL-1, IFN, and TNF may affect not the same but rather distinct neurons functionally connected to common pyrogenic effectors. Thus they suggest that differential neuronal substrates may be utilized by each cytokine to exert its pyrogenic effect.


1994 ◽  
Vol 22 (6) ◽  
pp. 454-461
Author(s):  
Marga Oortgiesen ◽  
Ruud Zwart ◽  
Henk P.M. Vijverberg

The effects of nitromethylene heterocycle (NMH) insecticides on subtypes of nicotinic acetylcholine (nACh) receptors were investigated in locust thoracic ganglion neurons, mouse N1E-115 neuroblastoma cells, and mouse BC3H1 muscle cells by using electrophysiological techniques. In locust neurons, all of the six NMH insecticides tested induced transient inward currents resembling nicotinic ACh-induced inward currents, while, in the continued presence of the NMH compounds, the ACh-induced inward current was blocked. The amplitude of the inward current and the blocking effects of the NMH insecticides were enhanced by concentrations between 0.1 and 10μM. Cross-desensitisation with the ACh-induced inward current confirmed that the NMH-induced inward current was governed by the activation of nACh receptors. Mammalian endplate type nACh receptors in BC3H1 cells and mammalian neuronal type nACh receptors in N1E-115 cells were much less sensitive to the NMH insecticides than the locust neuronal nACh receptors. At a concentration of 10μM, which blocked 80–100% of the ACh-induced inward current in locust neurons, NMH insecticides only partially blocked the ACh-induced inward currents mediated by the two subtypes of mammalian nACh receptors. NMH insecticides also failed to induce significant agonist effects in the mammalian cells at this concentration. The results provide a possible explanation for the selectively greater toxicity of NMH insecticides to insects than to vertebrates, at the level of nACh receptor subtypes and, hence, demonstrate that this in vitro approach is valuable for the investigation of species-specific interactions of compounds at their target site.


2002 ◽  
Vol 87 (5) ◽  
pp. 2398-2407 ◽  
Author(s):  
Carmen Cabanes ◽  
Mikel López de Armentia ◽  
Félix Viana ◽  
Carlos Belmonte

Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in vitro were used to characterize changes in membrane properties that take place from early postnatal stages (P0–P7) to adulthood (>P21). All neonatal TG neurons had uniformly slow conduction velocities, whereas adult neurons could be separated according to their conduction velocity into Aδ and C neurons. Based on the presence or absence of a marked inflection or hump in the repolarization phase of the action potential (AP), neonatal neurons were divided into S- (slow) and F-type (fast) neurons. Their passive and subthreshold properties (resting membrane potential, input resistance, membrane capacitance, and inward rectification) were nearly identical, but they showed marked differences in AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also segregated into S- and F-type groups. Differences in their mean AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and AHP duration were also prominent. In addition, axons of 90% of F-type neurons and 60% of S-type neurons became faster conducting in their central and peripheral branch, suggestive of axonal myelination. The proportion of S- and F-type neurons did not vary during postnatal development, suggesting that these phenotypes were established early in development. Membrane properties of both types of TG neurons evolved differently during postnatal development. The nature of many of these changes was linked to the process of myelination. Thus myelination was accompanied by a decrease in AP duration, input resistance ( R in), and increase in membrane capacitance (C). These properties remained constant in unmyelinated neurons (both F- and S-type). In adult TG, all F-type neurons with inward rectification were also fast-conducting Aδ, suggesting that those F-type neurons showing inward rectification at birth will evolve to F-type Aδ neurons with age. The percentage of F-type neurons showing inward rectification also increased with age. Both F- and S-type neurons displayed changes in the sensitivity of the AP to reductions in extracellular Ca2+ or substitution with Co2+ during the process of maturation.


Author(s):  
Dan Smelter ◽  
Mary Hayney ◽  
George Sakoulas ◽  
Warren Rose

Cefazolin and ertapenem has been shown to be an effective salvage regimen for refractory methicillin-susceptible Staphylococcus aureus bacteremia. Our findings suggest cefazolin plus ertapenem in vitro stimulates interleukin-1β release from peripheral blood monocytes both with and without S. aureus presence. This IL-1β augmentation was primarily driven by ertapenem. These findings support further exploration of cefazolin plus ertapenem in MSSA bacteremia and may partially explain its marked potency in vivo despite modest synergy in vitro .


1988 ◽  
Vol 255 (2) ◽  
pp. G184-G190 ◽  
Author(s):  
P. R. Wade ◽  
J. D. Wood

Intracellular recording methods were used in vitro to analyze the synaptic behavior of neurons in myenteric ganglia of guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs) were observed in a variety of types of colonic neurons. Both spontaneous and stimulus-evoked EPSPs were abolished or suppressed by addition of hexamethonium, tetrodotoxin, or elevation of Mg2+ and reduction of Ca2+ in the bathing medium. Individual neurons usually received inputs from several fiber tracts and multiple EPSPs were sometimes evoked by electrical stimulation of single-fiber tracts. Stimulus-evoked fast EPSPs were always of greater amplitude, longer duration, and longer decay time than were spontaneous fast EPSPs in the same neurons. No rundown of the fast EPSPs occurred during prolonged stimulation at frequencies up to 10 Hz. Repetitive stimulation evoked slow depolarizing potentials (slow EPSPs) in 25% of the neurons. Characteristics of the slow EPSPs were 1) slow rise times, 2) duration in the seconds time domain, 3) enhanced excitability, 4) increased input resistance, and 5) reduction of hyperpolarizing after-potentials. In general, the variety of synaptic potentials and the properties of the events were the same as found in myenteric neurons of the guinea pig small bowel. Compared with synaptic behavior of small intestinal myenteric neurons, the notable differences were absence of the rundown phenomenon for fast EPSPs in the colonic neurons and a greater incidence of spontaneously occurring fast EPSPs.


2000 ◽  
Vol 278 (3) ◽  
pp. L485-L491 ◽  
Author(s):  
Radhika Kajekar ◽  
Allen C. Myers

The effect of bradykinin on membrane properties of parasympathetic ganglion neurons in isolated guinea pig bronchial tissue was studied using intracellular recording techniques. Bradykinin (1–100 nM) caused a reversible membrane potential depolarization of ganglion neurons that was not associated with a change in input resistance. The selective bradykinin B2 receptor antagonist HOE-140 inhibited bradykinin-induced membrane depolarizations. Furthermore, the cyclooxygenase inhibitor indomethacin attenuated bradykinin-induced membrane depolarizations to a similar magnitude (∼70%) as HOE-140. However, neurokinin-1 and -3 receptor antagonists did not have similar inhibitory effects. The ability of bradykinin to directly alter active properties of parasympathetic ganglion neurons was also examined. Bradykinin (100 nM) significantly reduced the duration of the afterhyperpolarization (AHP) that followed four consecutive action potentials. The inhibitory effect of bradykinin on the AHP response was reversed by HOE-140 but not by indomethacin. These results indicate that bradykinin can stimulate airway parasympathetic ganglion neurons independent of sensory nerve activation and provide an alternative mechanism for regulating airway parasympathetic tone.


1995 ◽  
Vol 268 (1) ◽  
pp. R208-R213 ◽  
Author(s):  
J. G. Cannon ◽  
M. A. Fiatarone ◽  
M. Meydani ◽  
J. Gong ◽  
L. Scott ◽  
...  

Aging is associated with diminished immune function that may stem from alterations in arachidonic acid metabolism and lipid peroxidation. This study sought to determine if dietary modification of fatty acids influenced neutrophil and monocyte secretion after an in vivo inflammatory stress in older human subjects. Volunteers participated in protocols that forced their quadriceps muscles to lengthen during tension development (eccentric stress). These protocols can cause inflammatory foci in the muscle as well as alterations in circulating leukocyte function. In this study, in vivo neutrophil degranulation was assessed by plasma elastase concentrations, and mononuclear cell function was assessed by interleukin-1 beta (IL-1 beta) secretion in vitro. In response to eccentric stress, older subjects (> 60 yr old) taking a placebo had no apparent elastase response, whereas those taking fish oil supplements responded with a 142% increase in plasma elastase (P = 0.011), similar to responses of younger reference subjects (< 33 yr old) taking no supplement. Overall, elastase responses correlated with individual plasma arachidonic acid-to-eicosapentaenoic acid ratios (r = -0.881, P = 0.004). Thus apparent age-related differences in elastase release were reconciled by individual differences in fatty acid nutriture. No significant temporal changes in urinary lipid peroxide excretion or IL-1 beta secretion were observed; however, age-associated differences were found.


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