117,537 research outputs found
L-type calcium channel gating is modulated by bradykinin with a PKC-dependent mechanism in NG108-15 cells
No full textBradykinin (BK) excites dorsal root ganglion cells, leading to the sensation of pain. The actions of BK are thought to be mediated by heterotrimeric G protein-regulated pathways. Indeed there is strong evidence that in different cell types BK is involved in phosphoinositide breakdown following activation of G(q/11). In the present study we show that the Ca(2+) current flowing through L-type voltage-gated Ca(2+) channels in NG108-15 cells (differentiated in vitro to acquire a neuronal phenotype), measured using the whole-cell patch clamp configuration, is reversibly inhibited by BK in a voltage-independent fashion, suggesting a cascade process where a second messenger system is involved. This inhibitory action of BK is mimicked by the application of 1,2-oleoyl-acetyl glycerol (OAG), an analog of diacylglycerol that activates PKC. Interestingly, OAG occluded the effects of BK and both effects were blocked by selective PKC inhibitors. The down modulation of single L-type Ca(2+) channels by BK and OAG was also investigated in cell-attached patches. Our results indicate that the inhibitory action of BK involves activation of PKC and mainly shows up in a significant reduction of the probability of channel opening, caused by an increase and clustering of null sweeps in response to BK
Le collezioni di antichità: le raccolte dei Caetani dal XVIII secolo ad oggi
No full textAttraverso l’analisi dei documenti d’archivio e delle vecchie pubblicazioni si è tentato di ricostruire la storia della raccolta di antichità Caetani dal XVIII secolo ad oggi e si è individuata la provenienza da proprietà dei Caetani sia urbane – in particolare dalla Villa Caserta sull’Esquilino- sia extraurbane, di alcuni materiali attualmente conservati nel Palazzo romano alle Botteghe Oscure ; si è inoltre ricostruito il ruolo svolto da vari componenti della famiglia nella formazione della raccolta
Transition metal based Chemosensing Ensembles: ATP sensing in physiological conditions.
No full textSensing of biologically relevant anionic substrates in physiological conditions, employing the strategy of the chemosensing ensembles, is reported. Coordination of a fluorescent indicator to a dicopper(II) polyazamacrocyclic receptor ([Cu-2(L)]) results in the collapse of its fluorescence emission. Competitive binding of substrates for the receptor releases the indicator in solution, with full emission recovery. The spectral changes obtained for some indicators and substrates were analysed to determine their respective association constants for the receptor. Discrimination of micromolar ATP quantities from other interferents (small inorganic anions and well-known neurotransmitters) is improved by a judicious choice of the indicator, the resulting ATP sensor promising interesting biological applications
Chick RGS2L Demonstrates Concentration-Dependent Selectivity for Gq/11 and Gi/o Pathways that Inhibit L-type Calcium Channels
No full textIn neuronal cells, the influx of Ca2+ ions through voltage-dependent L-type calcium (L) channels
couples excitation to multiple cellular functions. In addition to voltage, several neurotransmitters,
hormones and cytokines regulate L channel gating via binding to G-protein-coupled receptors.
Intracellular molecules that modify G-protein activity – such as regulator of G-protein-signalling
(RGS) proteins – are therefore potential candidates for regulating Ca2+ influx through L channels.
Here we show that a novel RGS2 splice variant from chick dorsal root ganglion (DRG) neurons,
RGS2L, reduces bradykinin (BK)-mediated inhibition of neuronal L channels and accelerates
recovery from inhibition. Chick RGS2 reduces the inhibition mediated by both the pertussis toxin
(PTX)-sensitive (Gi/o-coupled) and the PTX-insensitive (presumably Gq/11-coupled) pathways.
However, we demonstrate for the first time in a living cell that the extent of coupling to each
pathway varies with RGS2L concentration. A low concentration of recombinant chick RGS2L
(10 nM) preferentially reduces the inhibition mediated by the PTX-insensitive pathway, whereas a
100-fold higher concentration attenuates both PTX-sensitive- and PTX-insensitive-mediated
components equally. Our data suggest that factors promoting RGS2L gene induction may regulate
Ca2+ influx through L channels by recruiting low-affinity interactions with Gi/o that are absent at
basal RGS2L levels
A yellow transient forms in the decomposition in acidic solution of the blue-violet nickel(II) complex of a trifurcated hexamine
No full textIn the decomposition in acidic solution of the octahedral high-spin nickel(II) complex with the hexamine sen, a thermodynamically unstable, kinetically controlled, square-planar low-spin species forms, with a lifetime of 5 s
Effetto della concentrazione del K+ sull'eccitabilità dei recettori ampollari
No full textIl polo "endolinfatico" delle cellule ciliate dell'orecchio interno si trova in contatto con un mezzo molto ricco in K+ (50-100 mM/l). Tuttavía non è ancora- chiarito se l'elevata concentrazione endolinfatica di K+ sia un fattore indispensabile per il mantenimento dell'eccitabilità di questi meccanorecettori. Quando i canali semicircolari isolati vengono immersi in una soluzione di Tyrode anfibi (KCl 2,6 mM/l) la scarica spontanea si riduce in modo considerevole; in minor misura anche la risposta alle deflessioni cupolari dei recettori ampollari risulta diminuita. L’eccitabilità tuttavia tende a ritornare alla norma se la concentrazione del KCl nel liquido di Tyrode viene aumentata di 2-4 volte. Se l'intero labirinto della rana viene posto in liquido di Tyrode, evitando l'apertura dei canali e quindi la penetrazione del liquido di Tyrode nel loro interno, l'eccitabilità dei recettori resta elevata; d'altra parte la scarica si innalza solo di poco quando il contenuto in K+ nel bagno viene aumentato di 2-4 volte.
I risultati indicano che la scarica dei recettori ampollari, in particolare quella di riposo, è notevolmente sensibile alle variazioni del contenuto in K+ del liquido che bagna il polo "endolinfatico" delle cellule.
Vengono avanzate alcune ipotesi sul possibile meccanismo d'azione de1 K+ a livello delle ciglia dei meccanorecettori
Modification of the skeletal muscle energy metabolism induced by intermittent normobaric hypoxia and treatment with biological pyrimidines
No full textMuscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analysed in normoxia and after normobaric intermittent hypoxia (12 hours continuously daily; for 5 days). Cytidine and/or uridine were administered daily at the dose of 120 mg/kg, i.p., 30 min before the beginning of the experimental hypoxia. The intermittent normobaric hypoxia induced a biochemical adaptation characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in the absence of significant changes in the Vmax of the tested muscle enzymes. In gastrocnemius muscle from hypoxic rats, the two biological pyrimidines tested induced various discrete, but often related, modifications of the contents of some Krebs cycle intermediates (i.e., alpha-ketoglutarate, malate) and related free amino acids (i.e., glutamate, alanine). In any case, the treatment with cytidine and/or uridine did not modify the Vmax of marker enzymes related to energy transductio
Recovery period after profound hypoglycemia. Influence of some metabolic modulators on the cerebral endogenous substrate utilization
No full textThe content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex after 20 min of severe hypoglycemia, followed by partial restitution during the recovery period. The adenine nucleotide pool remained reduced even if the energy charge returned to normal. During hypoglycemia the non-glucose endogenous substrates were provided by glycolytic intermediates, by Krebs' cycle intermediates and by related amino acids. Other substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20 min period of post-hypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, the amino acid pool size being still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency towards normalization of the free fatty acid cerebral content. During the post-hypoglycemic recovery, treatment with some specific metabolic modulators (i.e., uridine, L-acetylcarnitine, hopantenate, 6-amino-nicotinamide) suggests the possibility of an alternative cerebral substrate utilization due to the modulation of the cerebral biochemical machinery. Thus, increased carbohydrate utilization by hopantenate was consistent with decreased lipid breakdown, while increased carbohydrate utilization by uridine was concomitant with decreased amino acid degradation. On the other hand, decreased cerebral carbohydrate utilization by 6-aminonicotinamide was concomitant with increased lipid and amino acid breakdown. Furthermore, the increased loss of cerebral phospholipids and fatty acids by L-acetylcarnitine occurred in the presence of a large glucose availability and was concomitant with an extensive reduction on cerebral glycolytic flu
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