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N Stella

Publications and source records attributed to N Stella.

At least 19 recordsLinked to original sources
PubMed1999

Cannabinoid CB1 receptors and ligands in vertebrate retina: localization and function of an endogenous signaling system.

CB1, a cannabinoid receptor enriched in neuronal tissue, was found in high concentration in retinas of rhesus monkey, mouse, rat, chick, goldfish, and tiger salamander by using a subtype-specific polyclonal antibody. Immunolabeling was detected in the two synaptic layers of the retina, the inner and outer plexiform layers, of all six species examined. In the outer plexiform layer, CB1 was located in and/or on cone pedicles and rod spherules. Labeling was detected in some amacrine cells of all species and in the ganglion cells and ganglion cell axons of all species except fish. In addition, sparse labeling was found in the inner and/or outer segments of the photoreceptors of monkey, mouse, rat, and chick. Using GC/MS to detect possible endogenous cannabinoids, we found 3 nmol of 2-arachidonylglycerol per g of tissue, but no anandamide was detectable. Cannabinoid receptor agonists induced a dramatic reduction in the amplitude of voltage-gated L-type calcium channel currents in identified retinal bipolar cells. The presence and distribution of the CB1 receptor, the large amounts of 2-arachidonylglycerol found, and the effects of cannabinoids on calcium channel activity in bipolar cells suggest a substantive role for an endogenous cannabinoid signaling system in retinal physiology, and perhaps vision in general.

Animals↗
PubMed1998

Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle.

Mounting evidence from in vitro experiments indicates that lactate is an efficient energy substrate for neurons and that it may significantly contribute to maintain synaptic transmission, particularly during periods of intense activity. Since lactate does not cross the blood-brain barrier easily, blood-borne lactate cannot be a significant source. In vitro studies by several laboratories indicate that astrocytes release large amounts of lactate. In 1994, we proposed a mechanism whereby lactate could be produced by astrocytes in an activity-dependent, glutamate-mediated manner. Over the last 2 years we have obtained further evidence supporting the notion that a transfer of lactate from astrocytes to neurons might indeed take place. In this article, we first review data showing the presence of mRNA encoding for two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Second, by using monoclonal antibodies selectively directed against the two distinct lactate dehydrogenase isoforms, LDH1 and LDH5, a specific cellular distribution between neurons and astrocytes is revealed which suggests that a population of astrocytes is a lactate 'source' while neurons may be a lactate 'sink'. Third, we provide biochemical evidence that lactate is interchangeable with glucose to support oxidative metabolism in cortical neurons. This set of data is consistent with the existence of an activity-dependent astrocyte-neuron lactate shuttle for the supply of energy substrates to neurons.

Animals↗
PubMed1997

Functional role of high-affinity anandamide transport, as revealed by selective inhibition.

Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated. Anandamide inactivation is not completely understood, but it may occur by transport into cells or by enzymatic hydrolysis. The compound N-(4-hydroxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity anandamide accumulation in rat neurons and astrocytes in vitro, an indication that this accumulation resulted from carrier-mediated transport. Although AM404 did not activate cannabinoid receptors or inhibit anandamide hydrolysis, it enhanced receptor-mediated anandamide responses in vitro and in vivo. The data indicate that carrier-mediated transport may be essential for termination of the biological effects of anandamide, and may represent a potential drug target.

Analgesics↗
PubMed1997

A second endogenous cannabinoid that modulates long-term potentiation.

Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that contribute in important ways to the control of memory, cognition, movement and pain perception. Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences that include euphoria, analgesia, sedation and memory impairment. Although the pharmacology of cannabinoid drugs is now beginning to be understood, we still lack essential information on the endogenous signalling system(s) by which cannabinoid receptors are normally engaged. An endogenous ligand for cannabinoid receptors, anandamide, has been described. Here we report that sn-2 arachidonylglycerol (2-AG), a cannabinoid ligand isolated from intestinal tissue, is present in brain in amounts 170 times greater than anandamide. 2-AG is produced in hippocampal slices by stimulation of the Schaffer collaterals, an excitatory fibre tract that projects from CA3 to CA1 neurons. Formation of 2-AG is calcium dependent and is mediated by the enzymes phospholipase C and diacylglycerol lipase. 2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3-CA1 synapses. Our results indicate that 2-AG is a second endogenous cannabinoid ligand in the central nervous system.

Animals↗
PubMed1997

Interleukin-1 enhances the ATP-evoked release of arachidonic acid from mouse astrocytes.

During neuropathological states associated with inflammation, the levels of cytokines such as interleukin-1beta (IL-1beta) are increased. Several studies have suggested that the neuronal damage observed in pathogenesis implicating IL-1beta are caused by an alteration in the neurochemical interactions between neurons and astrocytes. We report here that treating striatal astrocytes in primary culture with IL-1beta for 22-24 hr enhances the ATP-evoked release of arachidonic acid (AA) with no effect on the ATP-induced accumulation of inositol phosphates. The molecular mechanism responsible for this effect involves the expression of P2Y2 receptors (a subtype of purinoceptor activated by ATP) and cytosolic phospholipase A2 (cPLA2, an enzyme that mediates AA release). Indeed, P2Y2 antisense oligonucleotides reduce the ATP-evoked release of AA only from IL-1beta-treated astrocytes. Further, both the amount of cPLA2 (as assessed by Western blotting) and the release of AA resulting from direct activation of cPLA2 increased fourfold in cells treated with IL-1beta. We also report evidence indicating that the coupling of newly expressed P2Y2 receptors to cPLA2 is dependent on PKC activity. These results suggest that during inflammatory conditions, IL-1beta reveals a functional P2Y2 signaling pathway in astrocytes that results in a dramatic increase in the levels of free AA. This pathway may thus contribute to the neuronal loss associated with cerebral ischemia or traumatic brain injury.

Adenosine Triphosphate↗
PubMed1997

Mechanism involved in initiation and propagation of receptor-induced intercellular calcium signaling in cultured rat astrocytes.

The mechanisms involved in the initiation and the propagation of intercellular calcium signaling (calcium waves) were studied in cultured rat astrocytes. The analysis of calcium waves, induced either by mechanical stimulation or by focal application of ionomycin, indicated that initiation was dependent on the presence of external calcium. In addition, pharmacological experiments indicate that intercellular propagation required PLC activation, integrity of IP3-sensitive internal calcium stores, and functional gap junctions. An extracellular action of ATP or glutamate and participation of voltage-dependent Ca2+ channels were tested by using enzymatic degradation, receptor antagonists, and channel blockers, respectively. Because neither the speed of propagation nor the extent of the calcium waves was affected by these treatments, these alternate mechanisms were excluded from playing a role in intercellular calcium signaling. Biochemical assays and focal applications of several agonists (methoxamine, carbachol, glutamate) of membrane receptors to neurotransmitters and peptides (endothelin 1) demonstrated that their ability to trigger regenerative calcium waves depended on phospholipase C activity and inositol phosphate production. Thus, in rat astrocytes, initiation and propagation of calcium waves involve a sequence of intra- and intercellular steps in which phospholipase C, inositol trisphosphate, internal calcium stores, and gap junction channels play a critical role. The identification of these different events allows us to determine several targets at which the level of long-range signaling in astrocytes may be controlled.

Animals↗
PubMed1996

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) potentiate the glutamate-evoked release of arachidonic acid from mouse cortical neurons. Evidence for a cAMP-independent mechanism.

Glutamatergic neurotransmission is associated with release of arachidonic acid (AA) from membrane phospholipids of both neurons and astrocytes. Since free AA has been shown to enhance glutamate-mediated synaptic transmission, it can be postulated that glutamate release and AA formation constitute a positive feed-back mechanism for sustained excitatory neurotransmission. In the present study, we examined whether the glutamate-evoked release of AA could be modulated by peptides. Using mouse cortical neurons in primary cultures, we show that the release of AA evoked by glutamate is potentiated by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide (PACAP). This effect is mediated through the activation of PACAP I receptors. However, several arguments show that this potentiating mechanism does not involve the cAMP/PKA pathway. 1) Increasing intracellular cAMP by either cholera toxin, forskolin, or 8-Br-cAMP treatments does not affect the glutamate-evoked release of AA; 2) potentiation of the glutamate response by PACAP is not prevented by the PKA inhibitor 8-Br-Rp-cAMPS. Also, an involvement of the phospholipase C protein kinase C pathways is unlikely since inhibitors of both phospholipase C (i.e. U-73122) and protein kinase C (i.e. Ro 31-8220) do not affect the potentiation of the glutamate response by PACAP. These observations indicate an effect mediated by PACAP I receptors, which does not involve the second messenger pathways classically associated with activation of this type of receptors. Furthermore, results indicate that this potentiating mechanism mediated by PACAP I receptor acts at a level downstream of the glutamate receptor-mediated calcium influx.

Animals↗
PubMed1996

Reduced glucose metabolism enhances the glutamate-evoked release of arachidonic acid from striatal neurons.

Glucose deprivation potentiates the glutamate receptor-evoked release of arachidonic acid from cultured mouse striatal neurons. In this study we investigated whether this potentiation would be modified by the end-products of glycolysis. These enhanced responses were completely reversed by the addition of increasing concentrations of either lactate or pyruvate. This reversal was not due to increased osmolarity as substituting sucrose for lactate or pyruvate did not mimic their effects. In contrast, in the presence of glucose, neither lactate nor pyruvate was effective. Furthermore, these monocarboxylic acids rescued neuronal respiration in the absence of glucose. Inhibiting glycolysis with iodoacetate in the presence of glucose reproduced the potentiated glutamate-evoked release of arachidonic acid observed following glucose deprivation and reduced neuronal respiration to the same extent as that observed in the absence of glucose. All of these effects were overcome by the addition of either lactate or pyruvate. The reversal of the potentiated glutamate-evoked release of arachidonic acid by lactate or pyruvate was inhibited by a specific inhibitor of monocarboxylic acid transport, alpha-cyano-4-hydroxycinnamic acid, suggesting that lactate and pyruvate act intracellularly. Therefore, we propose that the enhanced release of arachidonic acid evoked by glutamate during glucose deprivation results from reduced glycolysis and hence from a depletion of lactate or pyruvate.

Animals↗
PubMed1996

[Endovascular treatment of abdominal aorta aneurysms using the Stentor device. Preliminary experience].

PURPOSE: The aim of this report is to describe our experience with the Stentor device for endovascular treatment of the abdominal aortic infrarenal aneurysms also extending to the bifurcation and the common iliac arteries. Stentor is a thermal memory (Nitinol) self-expanding graft, covered by an external 0.1 mm Dacron material. METHODS: Between December 1994 and July 1995 endoluminal repair of infrarenal aneurysmal disease was undertaken in 6 patients at high surgical risk. The lesions include 2 infrarenal abdominal aorto-aortic aneurysms, 2 infrarenal abdominal aortic aneurysms extended to the common iliac arteries and 2 false aortic aneurysms in patients with previous aorto-bifemoral graft. Straight grafts were implanted in 4 patients and bifurcated in 2. Repair was done in the operating room using general anesthesia. The endograft was placed through remote arteriotomies and advanced under fluoroscopic guidance to his predetermined site. Three-dimensionally reconstructed spiral CT scan and arteriography were performed before the procedure for a preoperative accurate measurement for endograft preprocedural adaptation in length and diameter. RESULTS: All endografts were successfully deployed. Intraoperative arteriography at the end of the procedure revealed a distal "leak" into an aneurysmal common iliac artery, due to diameter mismatch, in a bifurcated device. There was no instance of embolism or graft migration. No patient required conversion to an open operation. There were no instances of embolism or graft migration. No patient required conversion to an open operation. There were no coagulative disorders. Minor complications were: groin haematoma (1), fever (1), intestinal paralysis (1), pelvic pain (1). Follow-up with spiral CT-scan and echo color-Doppler confirmed normal blood flow through the graft in 5 patients and persistence of distal leak in 1 patient. CONCLUSIONS: These preliminary results demonstrate the accuracy of implantation and device's adaptability to the particular anatomy of the aneurysmal aorta and iliac arteries. Proximal fixation to the aortic wall, secure seal at the proximal and distal fixation point present the critical aspects of this new surgical technique. More detailed preoperative measurements of aneurysmal disease are required rather than for traditional surgery. Presently we prefer to treat the no operable patients with this endovascular technique in relation with shortness of the follow-up.

Aged↗
PubMed1995

Modulation of the glutamate-evoked release of arachidonic acid from mouse cortical neurons: involvement of a pH-sensitive membrane phospholipase A2.

Excitatory synaptic transmission is associated with changes in both extracellular and intracellular pH. Using mouse cortical neurons in primary cultures, we studied the sensitivity of glutamate-evoked release of 3H-arachidonic acid (3H-AA) to changes in extracellular pH (pHo) and related intracellular pH (pHi). As pHo was shifted from 7.2 to 7.8, the glutamate-evoked release of 3H-AA was enhanced by approximately threefold. The effect of alkaline pHo on the glutamate response was rapid, becoming significant within 2 min. 3H-AA release, evoked by both NMDA and kainate, was also enhanced by pHo alkalinization. NMDA- and kainate-induced increase in free intracellular Ca2+ was unaffected by changing pHo from 7.2 to 7.8, indicating that the receptor-induced Ca2+ influx is not responsible for the pHo sensitivity of the glutamate-evoked release of 3H-AA. Alkalinization of pHi obtained by incubating neurons in the presence of HCO3- or NH4 enhanced the glutamate-evoked release of 3H-AA, while pHi acidification obtained by blockade of Na+/H+ and Cl-/HCO3- exchangers decreased the glutamate response. Membrane-bound phospholipase A2 (mPLA2) activity was stimulated by Ca2+ in a pH-dependent manner, increasing its activity as pH was shifted from 7.2 to 7.8. This pH profile corresponds to the pH profile of the glutamate-, NMDA- and kainate-evoked release of 3H-AA. Taken together, these results indicate that the glutamate-evoked release of 3H-AA may be mediated by the pH-sensitive mPLA2. Since excitatory neurotransmission mediated by glutamate results in both pHo and pHi changes and since AA enhances glutamatergic neurotransmission at both pre- and postsynaptic levels, the data reported here reveals a possible molecular mechanism whereby glutamate can modulate its own signalling efficacy in a pH-dependent manner by regulating the release of AA.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Glial receptors and their intervention in astrocyto-astrocytic and astrocyto-neuronal interactions.

As shown on cultured astrocytes from the mouse, in the presence of adenosine deaminase, 2-chloroadenosine by acting on A1-adenosine receptors potentiated the activation of phospholipase C induced by the alpha 1-adrenergic agonist, methoxamine. This potentiation required the presence of external calcium and was blocked by pertussis toxin. Moreover, this potentiation resulted from a cascade of events: activation (by calcium and protein kinase C) of a phospholipase A2 coupled to A1-adenosine receptors, release of arachidonic acid, which inhibited the reuptake of glutamate into astrocytes and finally additional activation of phospholipase C by externally accumulated glutamate through metabotropic receptors. The effects of 2-chloroadenosine and methoxamine were respectively mimicked by somatostatin and substance P while endothelins reproduced the combined effects of 2-chloroadenosine and methoxamine. Conditioned media from treated astrocytes enriched in glutamate stimulated phospholipase C in cultured striatal neurones. In addition, glutamate alone was also found to stimulate phospholipase A2 in astrocytes through receptors exhibiting a pharmacological profile distinct from metabotropic receptors coupled to phospholipase C and the glutamate response was potentiated by ATP. Moreover, the neuronal arachidonic acid production evoked by glutamate was potentiated by acetylcholine. Finally, the combined application of 2-chloroadenosine and methoxamine on striatal astrocytes reduced the permeability of gap junctions between astrocytes and this response was mimicked by arachidonic acid. Together, these results emphasized the contribution of astrocytes in the regulation of glutamatergic transmission.

2-Chloroadenosine↗
PubMed1994

Glutamate-evoked release of arachidonic acid from mouse brain astrocytes.

Brain astrocytes in primary culture from the rat or the mouse have been shown to possess ionotropic and metabotropic glutamatergic receptors. The activation of both types of receptors is responsible for a rise in the cytosolic concentration of calcium, while the stimulation of metabotropic receptors induces the accumulation of inositol phosphates. In the present study, it is demonstrated that in striatal astrocytes from mouse embryos, glutamate evokes a release of arachidonic acid. The nonionotropic receptors involved in this effect appeared to be pharmacologically distinct from those coupled to phospholipase C: (1) glutamate displayed different dose-response curves for the production of inositol phosphates (biphasic: EC50 = 25 and 300 microM) and the release of arachidonic acid (monophasic: EC50 = 200 microM); (2) L(+)-2-amino-4-phosphonobutyric acid (AP4) only antagonized the glutamate-evoked release of arachidonic acid without altering the production of inositol phosphates; (3) when used at a concentration of 0.1 mM, quisqualate induced a higher formation of inositol phosphates than glutamate (2 mM) while, in contrast to glutamate, it only weakly stimulated arachidonic acid release when used either at 0.1 mM or 1 mM. L(+)-2-amino-3-phosphonopropionic acid (AP3) suppressed both responses. The glutamate-evoked release of arachidonic acid seems to be oppositely regulated by protein kinases A and C. Indeed, the stimulation of adenylate cyclase by the beta-adrenergic agonist isoproterenol, vasoactive intestinal peptide, or pretreatment of striatal astrocytes with cholera toxin decreased the glutamate-evoked release of arachidonic acid. In contrast, ATP, which markedly stimulated inositol phosphate production, strongly potentiated the glutamate-evoked release of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Renal artery stenosis and aorto-iliac restoration: is it necessary to do extensive evaluation?].

In patients with aortoiliac disease and a stenosis of one or two renal artery, renal hypertension is rarely the sole mechanism of the elevated blood pressure. The preservation of nephron mass being the aim of the renal revascularization, we firmly believe that only three tests are required for the operative decision: renal ultrasonography, nephroscintigraphy and global and selective aortography.

Aorta↗
PubMed1993

Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Arachidonic acid (AA) has recently been shown to influence various cellular functions in the central nervous system. Here we report that AA increases, in a time- and concentration-dependent manner, 2-deoxy-D-[1-3H]glucose ([3H]2DG) uptake in primary cultures of astrocytes prepared from the cerebral cortex of neonatal mice. This effect is mimicked by an unsaturated fatty acid such as linolenic acid, while palmitic and arachidic acids, two saturated fatty acids, are inactive. Pharmacological agents that increase the endogenous levels of AA by stimulating AA release (melittin) or by inhibiting its reacylation (thimerosal) also promote [3H]2DG uptake by astrocytes. We also report that norepinephrine (NE) stimulates the release of [3H]AA from membrane phospholipids, with an EC50 of 3 microM; this effect is accompanied, with a temporal delay of approximately 4 min, by the stimulation of [3H]2DG uptake, for which the EC50 of NE is 1 microM. Since the cerebral cortex, the brain region from which astrocytes used in this study were prepared, receives a massive noradrenergic innervation, originating from the locus coeruleus, the effects of NE reported here further stress the notion that certain neurotransmitters may play a role in the regulation of energy metabolism in the cerebral cortex and point at astrocytes as the likely targets of such metabolic effects.

Animals↗