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1.
Int J Biol Macromol ; 266(Pt 2): 131314, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569995

RESUMO

Breeding of the black soldier fly is carried out to produce proteins. It is accompanied by releases during the life cycle of this insect. This work is a study of the valorization of these rejects through the production of chitins and chitosans with controlled characteristics. An extraction process is developed with an order of treatments and reaction conditions that provide chitins with high contents. These contents increase as the stages of the life cycle progress and drop for the adult. However, the exuviae chitins present organic impurities which will be eliminated at the N-deacetylation reaction for pupe and after a purification treatment for chitosan from larval stages. All these chitins have an α structure although certain physicochemical characteristics of the larval exuviae chitins are close to those presented by γ chitin. The observed shifts are linked to the effect of impurities rather than to a difference in structure. N-deacetylation of chitins makes possible the valorization of all rejects by the production of pure chitosans with high yields which retain a porous structure for the exuviae and fibrous for the adult which allow complementary applications. These chitosans are highly to completely deacetylated and their molar masses can vary depending on the process and life stage.


Assuntos
Quitina , Quitosana , Quitosana/química , Animais , Quitina/química , Dípteros/metabolismo , Dípteros/química , Dípteros/crescimento & desenvolvimento , Acetilação , Larva , Cruzamento , Estágios do Ciclo de Vida , Fenômenos Químicos
2.
J Dairy Sci ; 106(12): 9718-9732, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641336

RESUMO

This study aimed to determine whether 200 µg of GnRH (gonadorelin hydrochloride) would increase ovulatory response and pregnancies per artificial insemination (P/AI) compared with 100 µg at the first GnRH of the breeding-Ovsynch of a Double-Ovsynch program (DO) in lactating Holstein cows. Weekly cohorts of primiparous (n = 719) and multiparous (n = 1,191) cows submitted to DO (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH [G1], 7 d later PGF2α [PG1], 1 d later PGF2α, ∼32 h later GnRH [G2], and ∼16 h later timed artificial insemination [TAI]) for first service, randomly received either 100 µg or 200 µg of GnRH (gonadorelin hydrochloride) at G1 (primiparous, 64-75 DIM; multiparous, 59-70 DIM). Ovulation was determined by ultrasound 2 d after G1 (n = 1,294) and 2 d after G2 (n = 1,020). Blood samples were collected at G1 and at PG1 d to evaluate serum progesterone (P4) concentrations. Conventional (n = 314, Angus; n = 1,084, Holstein) and Holstein sexed semen (n = 276) were used. Pregnancy was diagnosed on d 32, 46, 88, and 200 post-TAI. The high dose of GnRH (200 µg) increased overall ovulatory response to G1 compared with 100 µg (81.3% vs. 65.1%), being similar between parities (primiparous, 72.2%; multiparous, 73.9%). Mean serum P4 concentrations at PG1 did not differ between treatments (100 µg: 9.59 ± 0.15 ng/mL vs. 200 µg: 9.43 ± 0.15 ng/mL). Cows with no ovulation to G1 had higher serum P4 concentrations at G1 than cows with ovulation to G1 (6.27 ± 0.19 ng/mL vs. 4.66 ± 0.07 ng/mL). At PG1, the proportion of cows with functional corpus luteum (98.7% vs. 89.7%) and serum P4 concentrations (9.68 ± 0.12 ng/mL vs. 9.14 ± 0.22 ng/mL) were greater in cows that ovulated to G1 compared with cows that did not ovulate. Also, cows that ovulated to G1 had a greater increase in serum P4 concentrations from G1 to PG1 than cows with no ovulation (5.26 ± 0.12 ng/mL vs. 3.32 ± 0.25 ng/mL). The high dose of GnRH improved overall P/AI at 32 d post-TAI in cows inseminated with conventional semen (54.6% vs. 48.2%) and tended to improve P/AI on 46 (48.8% vs. 44.9%), 88 (47.6% vs. 43.4%), and 200 (45.3% vs. 41.2%) d post-TAI. Primiparous cows inseminated with conventional semen had better P/AI than multiparous cows at d 32 (58.2% vs. 49.4%), 46 (55.1% vs. 44.4%), 88 (53.2% vs. 43.2%) and 200 (51.6% vs. 40.7%) post-TAI. Primiparous cows treated with 200 µg GnRH had lower P/AI on d 32, 46, 88, and 200 post-TAI when inseminated with sexed semen than with conventional semen. In summary, the higher dose of GnRH at G1 improved ovulatory response and P/AI at d 32 post-TAI and tended to improve P/AI at d 46, 88, and 200 post-TAI in cows inseminated with conventional semen. Moreover, the effect of treatment on P/AI in primiparous cows depended on semen type (conventional vs. sexed semen).


Assuntos
Lactação , Progesterona , Gravidez , Feminino , Bovinos , Animais , Lactação/fisiologia , Sincronização do Estro , Dinoprosta/farmacologia , Ovulação , Inseminação Artificial/veterinária , Hormônio Liberador de Gonadotropina/farmacologia , Fertilidade/fisiologia
3.
J Dairy Sci ; 104(7): 8290-8300, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33838886

RESUMO

Our objective was to compare the effect of treatment with GnRH at the first treatment (G1) of the Breeding-Ovsynch portion of a Double-Ovsynch (DO) protocol with human chorionic gonadotropin (hCG) on pregnancies per artificial insemination (P/AI) in lactating dairy cows. In experiment 1, lactating dairy cows (n = 1,932) submitted to a DO protocol for first timed artificial insemination (TAI) on 2 commercial dairy farms were blocked by parity (primiparous vs. multiparous) and were randomly assigned to receive 100 µg of GnRH versus 2,500 IU of hCG at G1. Overall, P/AI 39 d after TAI for cows inseminated with sexed dairy semen was greater for cows treated with GnRH than for cows treated with hCG within each parity (primiparous: 42.6% vs. 38.2%; multiparous: 39.4% vs. 30.3%). Similarly, P/AI 39 d after TAI for multiparous cows inseminated with conventional beef semen tended to be greater for cows treated with GnRH than for cows treated with hCG (41.1% vs. 34.3%). In experiment 2, lactating Holstein cows (n = 43) were blocked by parity and were randomly assigned to the treatment protocols described for experiment 1. Ovaries were evaluated with transrectal ultrasonography immediately before treatment and 24, 28, 32, 36, and 40 h after treatment to assess time from treatment to ovulation, and blood samples were collected immediately before G1, at the first PGF2α treatment, 8 and 16 h later, at the second PGF2α treatment, 8 and 16 h later, at the second GnRH (G2) treatment, and at TAI to compare luteolysis based on serum progesterone (P4) concentrations. Although mean (± standard error of the mean) time from treatment to ovulation was approximately 2 h greater for cows treated with hCG than for cows treated with GnRH (33.7 ± 0.6 vs. 31.5 ± 0.6 h), P4 concentrations during luteolysis and the proportion of cows with complete luteolysis (P4 <0.4 ng/mL at G2) did not differ between treatments. We conclude that replacing 100 µg of GnRH with 2,500 IU of hCG at G1 of a DO protocol decreased fertility to TAI in lactating dairy cows but did not affect the rate or completeness of luteolysis despite the increased interval from treatment to ovulation.


Assuntos
Sincronização do Estro , Hormônio Liberador de Gonadotropina , Animais , Bovinos , Gonadotropina Coriônica , Ensaios Clínicos Veterinários como Assunto , Dinoprosta , Feminino , Fertilidade , Inseminação Artificial/veterinária , Lactação , Ovulação , Progesterona
5.
J Hazard Mater ; 184(1-3): 710-716, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-20870356

RESUMO

This paper studied the efficiency of electrocoagulation/electroflotation in removing colour from synthetic and real textile wastewater by using aluminium and iron electrodes in an external-loop airlift reactor of 20 L. The disperse dye is a mixture of Yellow terasil 4G, Red terasil 343 150% and Blue terasil 3R02, the reactive dye is a mixture of Red S3B 195, Yellow SPD, Blue BRFS. For disperse dye, the removal efficiency was better using aluminium electrodes, whereas, the iron electrodes showed more efficiency for removing colour for reactive dye and mixed synthetic dye. Both for disperse, reactive and mixed dye, 40 mA cm(-2) and 20 min were respectively the optimal current density and electrolysis time. 7.5 was an optimal initial pH for both reactive and mixed synthetic dye and 6.2 was an optimal initial pH for disperse dye. The colour efficiency reached in general 90%. The results showed also that Red and Blue disappeared quickly comparatively to the Yellow component both for reactive and disperse dyes. The real textile wastewater was then used. Three effluents were also used: disperse, reactive and the mixture. The colour efficiency is between 70 and 90% and COD efficiency reached 78%. The specific electrical energy consumption per kg dye removed (E(dye)) in optimal conditions for real effluent was calculated. 170 kWh/kg(dye) was required for a reactive dye, 120 kWh/kg(dye) for disperse and 50 kWh/kg(dye) for the mixture.


Assuntos
Corantes/química , Eletroquímica/métodos , Poluentes Químicos da Água/química , Eletrodos , Indústria Têxtil
6.
Biomol Eng ; 24(5): 443-6, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17869177

RESUMO

Tribocorrosion is the term which describes the synergy between tribological and electrochemical processes. An apparatus was designed and built to study the tribocorrosion behavior of biomaterials. Electrochemical set-up with three electrodes is used for controlling the potential of the surface of a conducting material subjected to classical wear testing. Using this equipment, it is possible to carry out friction and wear tests in electrolytic solution under well-defined electrochemical conditions determined by the applied electrode potential. In this paper, this apparatus was described and the tests of deposited TiN on pure Ti for corrosion and tribocorrosion behavior under simulated body fluid were conducted. The presence of TiN layer on the surface of Ti has increased the open circuit potential. The charge transfer resistance (R(ct)) determined using electrochemical impedance spectroscopy (EIS) was higher for the nitrided surfaces than for the Ti substrates. However after wear test, R(ct) was significantly reduced because the protective layer was damaged.


Assuntos
Materiais Biocompatíveis/química , Eletroquímica/métodos , Teste de Materiais/métodos , Óxido de Alumínio/química , Impedância Elétrica , Eletroquímica/instrumentação , Teste de Materiais/instrumentação , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Propriedades de Superfície , Fatores de Tempo , Titânio/química
7.
Waste Manag ; 27(1): 89-95, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16497497

RESUMO

The thermal behaviour of chrome shavings and of sludges recovered after digestion of tanned wastes with Ca(OH)2 was studied. Ashes obtained after incineration of wastes at various temperatures were analysed by X-ray diffraction and EDX method. The main crystallized phases present in the ash obtained at 600 degrees C are Cr2O3 and NaCl. The diffractograms revealed an increase in the intensities of the chromium oxide peaks and a very notable decrease of the amount of sodium chloride at 1100 degrees C. EDX analysis revealed a total disappearance of the chlorine peak at this temperature. Scanning electron micrographs show that the waste lost its fibrous aspect when the temperature increases. Formation of aggregates was noted after 550 degrees C. Combustion of organic matters and decarbonation phenomenon are the main stages observed on GTA and DTA curves of sludges. These phenomena are, respectively, exothermic and endothermic. The diffractogram of sludges recorded at 550 degrees C, in the presence of a constant oxygen surplus, revealed the presence of CaCrO4 and CaCO3.


Assuntos
Hidróxido de Cálcio , Compostos de Cromo/química , Temperatura Alta , Eliminação de Resíduos , Esgotos/química , Carbonato de Cálcio/química , Compostos de Cálcio/química , Cromatos/química
8.
J Hazard Mater ; 145(1-2): 148-53, 2007 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-17157981

RESUMO

In this paper, the ability of chrome shavings to remove motor oils, oily wastes and hydrocarbons from water has been studied. To determine amount of hydrocarbons sorbed on tanned wastes, a FT-NIR methodology was used and a multivariate calibration based on partial least squares (PLS) was employed for data treatment. The light density, porous tanned waste granules float on the surface of water and remove hydrocarbons and oil films. Wastes fibers from tannery industry have high sorption capacity. These tanned solid wastes are capable of absorbing many times their weight in oil or hydrocarbons (6.5-7.6g of oil and 6.3g of hydrocarbons per gram of chrome shavings). The removal efficiency of the pollutants from water is complete. The sorption of pollutants is a quasi-instantaneous process.


Assuntos
Hidrocarbonetos/isolamento & purificação , Óleos Industriais/análise , Resíduos Industriais , Manufaturas , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Adsorção , Hidrocarbonetos/análise , Curtume , Poluentes Químicos da Água/análise
9.
J Hazard Mater ; 131(1-3): 73-8, 2006 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-16243434

RESUMO

Electrocoagulation method with iron electrode is used to treat the industrial textile wastewater in batch reactor. The effects of operating parameters such as time and potential electrolysis on the decolourization and COD removal efficiency have been investigated. The results indicate that electrocoagulation is very efficient and able to achieve 100% colour and 84% COD removal in 3 min at potential 600 mV. The effluent wastewater is very clear and its quality exceed the direct discharge standard. Furthermore, the mechanism of electrocoagulation is elucidated by zeta potential measurement.


Assuntos
Eletrocoagulação , Indústria Têxtil , Eliminação de Resíduos Líquidos/métodos , Corantes , Eletrólise , Estudos de Viabilidade , Compostos Férricos
10.
Anal Bioanal Chem ; 374(3): 540-6, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12373407

RESUMO

The ability of bone charcoal to remove Cr(III) from aqueous solutions by adsorption has been investigated. The adsorbent used was first characterised and then the adsorption was studied as a function of time and amount of charcoal. Tests were carried out with synthetic solutions whose Cr concentrations (500 mg L(-1)) were similar to those found in some effluents of Moroccan tannery industries. Cr removal efficiencies higher than 90% were obtained at pH 3.5 using 3 g of bone charcoal and a stirring time of about 30 min. Results of Cr removal by all sieved fractions of bone charcoal had shown the same interesting capabilities for Cr(III) retention. The cross interference with other elements was also investigated. Pre-treatment of bone charcoal by nitric acid led to an increase in its specific surface area but induced a drastic reduction in its Cr elimination abilities. Adsorption tests were also carried out using calcinated bone charcoal. The results obtained showed a similar percentage of Cr retention to those found with untreated bone charcoal. On the other hand, a double treatment of bone charcoal with HCl and NaOH provided an enhancement of Cr(III) retention. The role played by the mineral fraction of the solid phase of bone was thus evidenced.


Assuntos
Carvão Vegetal/química , Cromo/química , Resíduos Industriais , Poluentes Químicos da Água , Adsorção , Microscopia Eletrônica de Varredura , Marrocos , Espectrofotometria Atômica
11.
Mol Pharmacol ; 60(5): 999-1007, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11641428

RESUMO

Allosteric models of G protein-coupled receptors predict that G protein influences the spontaneous isomerization between inactive (R) and active (R*) conformations. Since inverse agonists have been proposed to preferentially bind to the inactive and uncoupled form(s), changes in the G protein content should influence the binding properties of these ligands. To test this hypothesis, we systematically assessed the effect of G proteins on the binding of beta(2)-adrenergic ligands with distinct levels of inverse efficacy. Recombinant baculoviruses encoding the human beta(2)-adrenoreceptor (beta(2)AR) were expressed alone or in combination with G protein subunits in Sf9 cells. Coexpression with the G protein alpha s beta 1 gamma 2 did not influence the relative efficacy of the ligands to inhibit the adenylyl cyclase but induced considerable decrease in number of sites detected by [(3)H]ICI 118551, [(3)H]propranolol, and (125)I-cyanopindolol. This loss was proportional to the inverse efficacy of the ligand used as the radiotracer in the assay. The addition of Gpp(NH)p inhibited the effects of G protein overexpression indicating that the G proteins acted allosterically. Consistent with this notion, Western blot analysis revealed that coexpression with the G proteins was not accompanied by a loss of immunoreactive beta(2)AR. Such allosteric effects of the G proteins were also observed in mammalian cells expressing endogenous level of G proteins indicating that the phenomenon is not unique to overexpression systems. Taken together, these results demonstrate that the apparent receptor number detected by radiolabeled inverse agonists is affected by the content in G proteins as a result of their influence on R/R* isomerization.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Receptores Adrenérgicos beta/metabolismo , Regulação Alostérica , Animais , Baculoviridae/genética , Células Cultivadas , Citometria de Fluxo , Proteínas de Ligação ao GTP/genética , Vetores Genéticos , Ligantes , Ensaio Radioligante , Spodoptera
12.
Mol Pharmacol ; 60(4): 816-27, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11562445

RESUMO

This study assessed the effects of short-term treatment (30-min) with inverse agonists on receptor protein levels and on the ability of agonists, inverse agonists, and neutral antagonists to bind to the human delta-opioid receptor (h delta OR). Incubation of human embryonic kidney 293s cells stably expressing h delta OR with the inverse agonist ICI174864 (1 microM) induced reciprocal changes in agonist and inverse-agonist binding. The total number of binding sites recognized by the agonists [(3)H]bremazocine and [(3)H][D-Pen(2),D-Pen(5)]-enkephalin was reduced by 33 and 57%, respectively, whereas binding capacity for the radiolabeled inverse-agonist [(3)H]Tyr-TicY[CH(2)NH]Cha-Phe-OH increased by 44%. In contrast, total receptor protein and sites labeled by neutral antagonists [(3)H]naltrindole and [(3)H]Tyr-D-Tic-Phe-Phe-OH remained unchanged. Pertussis toxin (PTX) and 5-guanylylimidodiphosphate (GppNHp) mimicked the outcome of ICI174864 pretreatment in promoting the loss of agonist binding sites. The lack of an additive effect on [(3)H]bremazocine binding when these three agents were combined indicates that inverse agonists may, in part, share the mechanism by which GppNHp and PTX reduce agonist binding capacity. Spontaneous recovery of maximal agonist binding capacity after inverse-agonist treatment was slow, suggesting a decrease in the isomerization rate between agonist- and inverse agonist-preferring conformations. Overall, the data presented are consistent with the idea that h delta ORs exist in multiple states capable of discriminating among ligands of different levels of efficacy and show that, after short-term treatment with an inverse agonist, the receptor ability to adopt conformations preferentially induced by agonist ligands is reduced.


Assuntos
Analgésicos/farmacologia , Benzomorfanos/farmacologia , Encefalina Leucina/farmacologia , Antagonistas de Entorpecentes/farmacologia , Receptores Opioides delta/metabolismo , Sítios de Ligação/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/metabolismo , Encefalina Leucina/análogos & derivados , Humanos , Conformação Proteica , Ensaio Radioligante , Receptores Opioides delta/agonistas , Receptores Opioides delta/antagonistas & inibidores , Trítio
13.
J Neurochem ; 71(3): 1158-67, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9721741

RESUMO

The purpose of the present study was to investigate the effects of repeated administration of the neurotensin receptor antagonist, SR 48692, on the activity of the mesocortical and mesolimbic dopaminergic (DA) systems. We showed that daily administration of SR 48692 for 15 days (1 mg/kg i.p.) to Wistar rats increased the expression of tyrosine hydroxylase mRNA and protein in the ventral mesencephalon. Simultaneous in vivo microdialysis in the shell part of the nucleus accumbens (AcbSh) and the medial prefrontal cortex (mPFC) revealed that blockade of neurotensin receptors for 15 days decreased basal extracellular levels of DA (approximately 50%) and its metabolites in the AcbSh, whereas no modification in DA levels was observed in the mPFC. In animals submitted to a forced swimming stress, which preferentially enhanced extracellular DA levels in the mPFC, treatment with SR 48692 failed to affect the stress-induced increase in DA. Moreover, given that glucocorticoids can modulate the activity of mesencephalic DA neurons, we examined the effect of the same SR 48692 treatment on corticosterone levels in dialysates from the AcbSh. We found that repeated SR 48692 did not affect the basal levels of free corticosterone, but significantly reduced the increase induced by forced swimming stress. The present results demonstrate that repeated treatment with SR 48692 modulates selectively the DA mesolimbic system when compared with the mesocortical pathway. These findings suggest that long-term treatment with selective neurotensin receptor antagonists could have potential clinical utility in the treatment of neuropsychiatric disorders associated with hyperactivity of the mesolimbic DA systems or the hypothalamic-pituitary-adrenal axis.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Dopamina/fisiologia , Sistema Límbico/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , Pirazóis/administração & dosagem , Quinolinas/administração & dosagem , Receptores de Neurotensina/antagonistas & inibidores , Animais , Córtex Cerebral/fisiologia , Corticosterona/metabolismo , Espaço Extracelular/metabolismo , Sistema Límbico/fisiologia , Masculino , Mesencéfalo/fisiologia , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Pirazóis/farmacologia , Quinolinas/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Estresse Fisiológico/metabolismo , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/genética
14.
Trends Pharmacol Sci ; 18(10): 372-86, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9357322

RESUMO

The recent development of selective and highly potent nonpeptide antagonists for peptide receptors has constituted a major breakthrough in the field of neuropeptide research. Following the discovery of the first nonpeptide antagonists for peptide receptors ten years ago, numerous other antagonists have been developed for most neuropeptide families. These new, metabolically stable compounds, orally active and capable of crossing the blood-brain barrier, offer clear advantages over the previously available peptide antagonists. Nonpeptide antagonists have provided valuable tools to investigate peptide receptors at the molecular, pharmacological and anatomical levels, and have considerably advanced our understanding of the pathophysiological roles of peptides in the CNS and periphery. Evidence from animal and clinical studies suggests that nonpeptide antagonists binding to peptide receptors could be useful for the treatment of disease states associated with high levels of neuropeptides. In this article Catalina Batancur, Mounia Azzi and William Rostène will address the recent developments in nonpeptide antagonists for neuropeptide receptors, with a particular focus on their CNS actions.


Assuntos
Receptores de Neuropeptídeos/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Humanos , Dados de Sequência Molecular , Receptores de Neuropeptídeos/química , Receptores de Taquicininas/antagonistas & inibidores , Receptores de Taquicininas/química
16.
Brain Res Mol Brain Res ; 42(2): 213-21, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9013776

RESUMO

Adaptive changes in brain neurotensin (NT) receptors were investigated in rats after repeated administration of SR 48692, a potent and selective non-peptide NT receptor antagonist. Administration of SR 48692 (1 mg/kg i.p.) for 15 days did not alter NT content in the brain but highly enhanced the expression of NT receptor mRNA as shown by quantitative in situ hybridization. The increase of the signal was observed in numerous areas of the brain, such as the anterior cingulate, perirhinal and retrosplenial cortices, the suprachiasmatic nucleus, the ventral tegmental area, the substantia nigra and the posterior cortical nucleus of the amygdaloid complex. Moreover, the SR 48692 treatment induced the expression of NT receptor mRNA in several nuclei of the diencephalon where it could not be detected in basal conditions. Immunoblot analysis with a specific antibody directed against the rat cloned NT receptor revealed an important increase in NT receptor protein in the brain of SR 48692-treated rats, correlating well with the increase in NT receptor mRNA levels. Surprisingly, the number and the affinity constant of NT binding sites determined on brain membrane homogenates remained unchanged after SR 48692 treatment, even after membrane permeabilization with low concentrations of digitonin. These results suggest that chronic treatment with a specific NT antagonist induces an up-regulation of NT receptors at the level of mRNA and protein. Moreover, they indicate that after a chronic treatment with SR 48692, the number of NT binding sites remains stable in contrast to what is observed after 5-day treatment or with central monoaminergic receptor following their long-term blockade.


Assuntos
Encéfalo/efeitos dos fármacos , Pirazóis/farmacologia , Quinolinas/farmacologia , Receptores de Neurotensina/antagonistas & inibidores , Animais , Hibridização In Situ , Masculino , Proteínas/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo
17.
Neurosci Lett ; 172(1-2): 97-100, 1994 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-8084546

RESUMO

In the present study, we examined the regulation of neurotensin receptor following a chronic pharmacological blockade of the neurotensin transmission with a nonpeptide neurotensin receptor antagonist, SR 48692. Our results showed that treatment of the rats for five days with SR 48692, at a dose of 1 mg/kg, i.p., induced an increase of both the number of binding sites for 125I-neurotensin to whole brain membrane homogenates and neurotensin receptor mRNA levels in the ventral mesencephalon. This study brings the first evidence for an in vivo up-regulation of neurotensin receptors following their pharmacological blockade, and suggests that endogenous neurotensin exerts a tonic inhibitory control on neurotensin receptor mRNA levels.


Assuntos
Química Encefálica/efeitos dos fármacos , Pirazóis/farmacologia , Quinolinas/farmacologia , Receptores de Neurotensina/antagonistas & inibidores , Receptores de Neurotensina/biossíntese , Animais , Autorradiografia , Ligação Competitiva/efeitos dos fármacos , Densitometria , Hibridização In Situ , Técnicas In Vitro , Radioisótopos do Iodo , Masculino , Membranas/efeitos dos fármacos , Membranas/metabolismo , Neurotensina/farmacocinética , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar
18.
Eur J Pharmacol ; 255(1-3): 167-74, 1994 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8026542

RESUMO

Neurotensin has been suggested to be involved in neurological and mental disorders associated with altered dopaminergic transmission. The lack of a potent neurotensin receptor antagonist had prevented us from studying the real physiological implication of this peptide in brain function. We thus recently developed such a non-peptide neurotensin receptor antagonist, SR 48692, (2-(1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole- 3-carbonyl)amino)-adamantane-2-carboxylic acid), which appeared to be potent in various central and peripheral preparations. In the present study, we tested the pharmacological properties of SR 48692 and of two optically synthetic analogs of this compound on neurotensin binding to both adult guinea-pig brain membrane homogenates and coronal brain sections, as well as on neurotensin stimulation of the K(+)-evoked release of [3H]dopamine in guinea-pig striatal slices. Our results demonstrated that (1) high-affinity neurotensin binding sites are present in the guinea-pig brain in regions rich in both dopamine cell bodies and terminals; (2) the binding of neurotensin is inhibited by SR 48692 and its related S(+) active analog, SR 48527, with IC50 values in the nM range and (3) the non-peptide antagonist has no agonist effect but antagonizes neurotensin-induced [3H]dopamine release from guinea-pig striatal nerve terminals.


Assuntos
Química Encefálica/efeitos dos fármacos , Dopamina/metabolismo , Receptores de Neurotensina/efeitos dos fármacos , Animais , Autorradiografia , Cobaias , Técnicas In Vitro , Radioisótopos do Iodo , Masculino , Membranas/efeitos dos fármacos , Membranas/metabolismo , Neurotensina/metabolismo , Potássio/farmacologia , Pirazóis/farmacologia , Quinolinas/farmacologia , Receptores de Neurotensina/antagonistas & inibidores
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