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Biomedical subjects

G Simonnet

Publications and source records attributed to G Simonnet.

At least 73 records · Page 4Linked to original sources

[Angiotensin II and nigostriatal system (author's transl)].

The central renin-angiotensin system is implicated most importantly in the control of water balance, blood pressure and endocrine function (AVP and ACTH). Several central structures are sensitive to angiotensin II (A II), principally: the subfornical organ, the vascular organ of the lamina terminalis, the area postrema and the preoptic area. Furthermore, binding studies with radio-active ligands and also immunohistofluorescence have shown respectively the presence of A II receptors and immunoreactive material bound by A II antibodies in other central structures, and in particular parts of the motor system. In the present study, a double approach, both electrophysiological and biochemical, was used to investigate the possible role of the peptide A II in the neostriatum of the rat. 1 Microiontophoretic application of A II was shown to modify the spontaneous activity of some neurones (15/68) in the neostriatum. Generally, the action of A II was inhibitory and the inhibition was blocked by Sar1-Ileu8-A II, a specific A II antagonist. 2 Angiotensin II 10(-6) M; 10(-5) M; 5.10(-5) M) stimulated the spontaneous release of 3H-dopamine continuously synthetized from 3H-tyrosine in striatal slices of the rat. The A II-evoked release of 3H-dopamine was prevented when slices were superfused with a calcium-free medium containing EGTA. It was also suppressed in the presence of the specific antagonist Sar1-Ileu8-A II. 3 Kainic acid lesion of the intrastriatal cell bodies produced a moderate decrease of A II in the striatum (38%) whilst the activity of the converting enzyme decreased dramatically (-68%). These results suggest that there are angiotensin-containing nerve endings in the neostriatum, and that the cell bodies of such nerves are located outside this structure. Their functional role is discussed.

Angiotensin II↗

Evidence of a direct action of angiotensin II on neurones in the septum and in the medial preoptic area.

Angiotensin II (AII) was microiontophoretically applied on neurones located in the septum and the medial preoptic area (MPOA). All the septal neurones sensitive to AII (15/37) responded by an inhibition to the peptide application. Of 44 units tested in the MPOA 21 cells (48%) were sensitive to AII and responded either by an increase (11/21) or decrease (10/21) in their firing. The specificity of these responses were ascertained by simultaneous application of the antagonist Sar-Ile-Angiotensin II. These data suggest that Angiotensin II acts directly on neurones of the septum and medial preoptic area, structures implicated in the control of drinking behaviour.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Effect of nerve activity on the in vivo release of [3H]serotonin continuously formed from L-[3H]tryptophan in the caudate nucleus of the cat.

A new isotopic approach has been developed to study the in vivo release of serotonin (5-HT). 'Encéphale isolé' cats were implanted with a push-pull cannula in the ventrocaudal part of the head of the caudate nucleus to estimate the release of [3H]5-HT continuously synthesized from L-[3H]tryptophan. Both [3H]5-HT and [3H]tryptamine were found in superfusates. Resting steady state in the release of [3H]indoleamines was observed as soon as 20 min after the beginning of the superfusion with L-[3H]tryptophan; the levels of [3H]5-HT in superfusates were 2.5 times those of [3H]tryptamine and about 6 times the blank value. They were markedly enhanced in the presence of fluoxetine (5 x 10(-6)M), a blocker of the 5-HT uptake process. A marked increase in the release of [3H]5-HT was seen during the local depolarization of 5-HT terminals with potassium chloride (60 mM) or batrachotoxin (10(-6)M) or during the stimulation of 5-HT cell bodies in the nucleus raphe dorsalis with L-glutamic acid (5 x 10(-5)M). These treatments did not enhance the efflux of [3H]tryptamine. The potassium-evoked release of [3H]5-HT was reduced by LSD (10(-5)M). LSD added alone in the superfusing fluid was without effect. The batrachotoxin-evoked release of [3H]5-HT was inhibited in the presence of tetrodotoxin (9 x 10(-6)M). The spontaneous release of [3H]5-HT and [3H]tryptamine was markedly reduced in the presence of a calcium-free medium containing cobalt (10 mM). A transient slight reduction in the spontaneous release of [3H]5-HT was observed in the presence of tetrodotoxin (9 x 10(-6)M). The local cooling of 5-HT cell bodies with a cryoelectrode induced a slight reversible decrease in [3H]5-HT release. These last two treatments were without significant effect on [3H]tryptamine efflux in superfusates. These results indicate that the release of [3H]5-HT endogenously formed from [3H]tryptophan is dependent on nerve activity and that this is not the case for [3H]tryptamine. The advantages of the isotopic approach for in vivo studies on the release of 5-HT are discussed.

Animals↗

Stimulating effect of angiotensin II on the spontaneous release of newly synthetized [3H]dopamine in rat striatal slices.

Angiotensin II (A II) (10(-6) M, 10(-5) M, 5 . 10(-5) M) stimulated the spontaneous release of [3H]dopamine (DA) continuously synthetized from [3H]tyrosine in striatal slices of the rat. The A II-evoked release of [3H]-DA was prevented when slices were superfused with a calcium-free medium containing EGTA 5 . 10(-4) M. It was also suppressed in the presence of the potent antagonist Sar1-Ile8-angiotensin.

Angiotensin II↗

Vasopressin release and drinking induced by intracranial injection of angiotensin II in monkey.

The effects of intracerebral injection of angiotensin II (AII) on both water intake and arginine-vasopressin (AVP) release were tested on unanesthetized rhesus monkeys (Macaca mulatta). Injection of 10(-10) mol of peptide was administered with a cannula microinjection system stereotaxically implanted into different diencephalic structures. The preoptic area, anterior part of third ventricle, caudate nucleus, and septum appeared to be the injection sites most effective in eliciting both drinking behavior and AVP release when the animal did not have access to water. On the contrary, when water was presented, AVP release was blocked after AII microinjections in the preoptic area and the third ventricle. No drinking was observed after microinjection in the supraopticus nucleus although AVP release was stimulated. These data suggest that AII might be effective in the regulation of water balance by centrally controlling both the input (drinking) and the output (ADH secretion) of water.

Angiotensin II↗

Characteristics of the activation by dithiothreitol and Fe(2+) of tryptophan hydroxylase from the rat brain.

The preincubation of tryptophan hydroxylase extracted from various areas of the central nervous system of the rat with 30 mM dithiothreitol and 50 muM ferrous ammonium sulfate under nitrogen atmosphere resulted in a persistent increase of its activity. Studies on the enzyme characteristics indicated that this activation was associated with a doubling in its Vmax and a shift (from 7.6 to 7.2) of the optimal pH for its activity. In contrast, the molecular weight and the apparent affinities of tryptophan hydroxylase for its pterin cofactor and for tryptophan were not significantly altered by the preincubation with dithiothreitol and ferrous ammonium sulfate. Since this treatment did not prevent the stimulatory effects of various compounds (phosphatidylserine, ATP and MG(2+), Ca(2+)) on tryptophan hydroxylase activity, this might be a good procedure to activate this enzyme with only minor changes in its regulatory properties.

Animals↗

Calcitonin diuretic effect in the rabbit.

In an attempt to study the renal effects of Calcitonin (porcine CT) in the rabbit, the excreted fractions of filtered water, osmolality, sodium, potassium and chloride, and the calcium and phosphorus urinary excretions were studied during isotonic (ISD) and hypertonic (HSD) saline diuresis. Four doses (0.1, 0.8, 4 and 20 IU MRC/kg were perfused during one hour in I.S.D.; 4 and 20 IU MRC/kg in HSD. During ISD, Calcitonin at doses of 4 and 20 IU MRC/kg/hr significantly increased the diuresis and the Na+, Cl-, K+, PO4 3-, Ca2+ excreted fractions. This effect was also observed, to a lesser extent, at a dose of 0.8 IU MRC/kg/hr, whereas 0.1 IU MRC/kg/hr produced no significant effect. During ISD, a log dose related effect of CT appeared to exist with all studied parameters. Moreover, a biphasic pattern of free-water clearance was observed during ISD: this parameter increased during the first half hour of CT perfusion, and then decreased dramatically. During HSD, CT perfusion induced a decrease of free-water reabsorption and urinary osmolality/plasma osmolality ratio. These results suggest that the diuretic effect and saliuretic effect of CT (in the rabbit) are mainly the consequence of the decrease of the proximal reabsorption of sodium. The possibility of a second site of action is discussed. The diuretic effects of CT are compared to data observed with the well-known diuretic drugs.

Animals↗

[Diuretic action of calcitonin: demonstration of an inhibiting effect on sodium reabsorption in the ascending limb of Henlé's loop].

It was found that calcitonin (porcine) at the dose: 4 I.U. MRC./kg/hr (i.v.), in the rabbit, increased the diuresis and oxmolal excretion, and simultaneously decreased free-water reabsorption and urinary osmolality. The results suggest that calcitonin acts by inhibiting sodium reabsorption in the ascending limb of Henl's loop. This hypothesis was confirmed by renal autoradiography study with 22Na.

Animals↗

Solubilization and characterization of covalently labeled angiotensin II receptors in cultured mouse spinal cord cells.

To investigate the physicochemical characteristics of angiotensin II receptors in nervous tissue, [125I]-labeled AII was covalently linked to its binding sites in cultured mouse spinal cord cells, using the chemical crosslinking agent disuccinimidyl suberate. The liganded complexes were analyzed by SDS/polyacrylamide gel electrophoresis. Autoradiograms revealed a single band which corresponding to a component with a calculated Mr value of 68,000 +/- 5,000. The same radioactive band was observed under reducing or non-reducing conditions, although in the presence of beta-mercaptoethanol the band was less intense. This suggests that the AII binding unit may contain essential disulfide bonds close to the AII binding site. After solubilization with 1% Triton X-100, extracts were analyzed by HPLC gel filtration. Three radioactive species were identified with apparent molecular weights of 65,000; 115,000 and 185,000. Results obtained in the presence or absence of 10 nM unlabeled AII showed that these three units were common to both the high and the low affinity binding sites. The results also demonstrate that AII receptors in nervous tissue have similar physicochemical properties to those from other tissues, and that the 68,000 subunit probably contains the AII binding site.

Angiotensin II↗

Electrophysiological effects of FLFQPQRF amide, an endogenous brain morphine modulating peptide, on cultured mouse spinal-cord neurons.

Intracellular recordings were made from dissociated fetal mouse spinal cord neurones in primary culture. Micropressure application of FLFQPQRFamide (10(-5) M in the delivery pipette), an endogenous mammalian brain morphine modulating peptide, onto the surface of spinal cord neurones induced, in a dose dependent manner, a transitory hyperpolarization followed by a long lasting depolarization of the membrane potential (n = 37). In contrast, no response was observed when the peptide was applied on dorsal root ganglia neurones (n = 30). The depolarizing phase of this response was underlied by an increase of the input resistance. Extrapolated reversal potential for the depolarizing phase was close to -80 mV while it was close to -40 mV for the hyperpolarizing phase. Increasing extracellular K+ concentration raised the reversal potential value of depolarizing phases to more positive values. The amplitude of the depolarizing phase was reduced by application of tetraethylammonium (50 mM) while it was enhanced by application of 4-aminopyridine (3 mM). CaCl2 application (3 mM) reversibly blocked the hyperpolarization and decreased the subsequent depolarization. In presence of Ba2+ the extrapollated reversal potential of the hyperpolarizing phase was dramatically shifted to a more positive value. Finally FLFQPQRFamide induced response can be partially mimicked by FMRFamide application. Our observations indicate that FLFQPQRFamide can have multiple effects on membrane conductance of mammalian spinal cord neurones by acting on a single class of receptor. These effects of FLFQPQRFamide were found to be mainly excitatory.

Animals↗

Biphasic effect on nociception and antiopiate activity of the neuropeptide FF (FLFQPQRFamide) in the rat.

The purpose of the present study was to systematically investigate the effects of the mammalian neuropeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) on nociception, using the tail-flick test. We report that ICV administration of NPFF induces a rapid and short-lasting hyperesthesic effect during day or night, for doses ranging from 10 ng to 10 micrograms. During the night, this hyperesthesic effect is followed by a long-lasting analgesic effect, the magnitude of which is related to the magnitude of the hyperesthesic effect. In addition to this intrinsic effect of NPFF, we report that NPFF reverses morphine-induced analgesia and that the magnitude of the response elicited by NPFF increases as a function of morphine-induced analgesia.

Amino Acid Sequence↗

NPFF, a FMRF-NH2-like peptide, blocks opiate effects on ileum contractions.

We studied the ability of NPFF, a FMRFamide-like peptide with certain antiopiate properties, to affect the inhibitory effect of morphine on the electrically induced contraction of guinea pig ileum. Neuropeptide FF had no effect when administered alone but reduced morphine inhibition in a noncompetitive manner. Neuropeptide FF also altered the inhibitory effect of opioid peptides as released by an intense electrical stimulation at 10 Hz. These results suggest that NPFF receptors exist in guinea pig ileum in association with opiate receptors, and that endogenous NPFF may play a role in the diarrhea observed in the morphine withdrawal syndrome.

Animals↗

Double-blind study of effects of enkephalinase inhibitor on adverse reactions to myelography.

The side effects in myelography are well known and frequently observed. The most common are headache, nausea, and vomiting. In this study, a rather new compound, Thiorphan, was examined, which displays an antinociceptive activity by inhibiting enkephalinase activity. Forty-two patients received intravenous infusions of Thiorphan before myelography. Another 42 patients were in a control group, and Thiorphan was not administered. In the treated group, postmyelographic headache was found in 24% (versus 52% in the control group). Nausea and vomiting were never seen. Low back pain or sciatica was diminished in 33% of cases. Enkephalin levels in cerebrospinal fluid were measured by a radioreceptor-assay method in both groups without any correlation.

Adolescent↗

[Clofoctol binding by the bacteria (author's transl)].

Clofoctol is an antibacterial agent which is active only on Gram + bacteria. The clofoctol binding on bacteria is fast and the number of molecules bound is about 10(6) to 1,5 10(7) molecules per bacteria. Bacteria sensitivity towards clofoctol is the result of their ability to bind with it. Gram negative and Gram + protoplasts of bacteria bind the clofoctol. Binding of clofoctol by B. subtilis is obtained with viable cells and also with thermal inactivated cells. Binding of clofoctol by the cells is reversible and we showed that the 14C clofoctol used for the experiments and the unlabelled clofoctol have the same behaviour. ions as K+, Mg++, Ca++, Mn++, and Fe++, pH variation between 2 to 9, and urea have no influence on the binding of clofoctol by the bacteria, but, sodium lauryl sulfate is an inhibitor of the binding. These results mean that clofoctol bounds are made by hydrophobic links.

Anti-Bacterial Agents↗