Dissertations / Theses on the topic 'Arginine vasopressine [AVP]'

Deux composés benzéniques poly-substitués par des groupes pyrroliques, le 1,3,5-tripyrrolylbenzène et l'hexapyrrolylbenzène, ont étés utilisés comme réactifs de synthèse de semi-conducteurs organique p-conjugué. Le couplage des groupes pyrroliques du 1,3,5-tripyrrolylbenzène est intermoléculaire et conduit à la formation d'un polymère organique p-conjugué tandis qu'il est pour l'hexapyrrolylbenzène intramoléculaire de type radical-cation substrat et conduit à la formation de molécules discoi͏̈des qui s'assemblent en matériau organique conducteur p-empilé. Notre approche a permis de dégager des critères structuraux pour les molécules réactives permettant de contrôler la nature (polymère-p ou matériau p-empilé) du semi-conducteur organique produit
Two pyrrolyl poly-substituted benzene compounds, 1,3,5-tripyrrolylbenzene and hexapyrrolylbenzene, were used as reagents in the synthesis of p-conjugated organic semi-conductors. In the case of 1,3,5-tripyrrolylbenzene, the coupling of the pyrrolyl moieties is intermolecular and yields a p-conjugated organic polymer, while in the case of hexapyrrolylbenzene it is intramolecular and yields discotic molecules which self-assemble in a p-stacked material. The study leads to structural criteria for reagent molecule that determine the kind (p-conjugated polymer or p-stacked material) of organic semi-conductor produced

The association between selective serotonin reuptake inhibitors (SSRis) and hyponatraemia has been well documented, the elderly appearing to be at greatest risk. An analysis of data of hyponatraemia in the elderly using SSRis from all published cases and from the Committee on Safety of Medicines found that the mean time to detection was about 3 weeks after commencing SSRis. A wide range of time to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is detected by chance rather than being specifically looked for. This is probably a sporadic, idiosyncratic phenomenon that is not dose related as A VP function determined by serum and urine concentrations was found to be normal in six elderly patients using sertraline. In the elderly there are physiological changes, a high prevalence of medical illnesses and concomitant drug use which may precipitate hyponatraemia. Together with a risk of altered water regulation in psychiatric illness this may account for the particular susceptibility of this group to hyponatraemia whilst using SSRis. AIMS & HYPOTHESIS: This dissertation will explore the physiology of Arginine V asopressin and how changes in this system along with other physiological changes in the elderly make the elderly susceptible to hyponatraemia. This problem will then be explored in the context of elderly people with depression using SSRis which are known to cause hyponatraemia. In the first part of the research section the aims are to report the published cases of hyponatraemia occurring whilst using SSRis from the United Kingdom and specifically focus on cases in people 60 years and older. Secondly to re-analyse all case reports in the literature looking only at this population. The third aim was to investigate whether dysregulation of vasopressin function in the elderly using SSRis is a sporadic or usual phenomenon. The null hypothesis is that A VP function is not disturbed by SSRis.

Background: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease with symptoms of polydipsia, polyuria and dehydration caused by arginine vasopressin deficiency. Disease onset is within infancy or adolescence. A variety of disease-causing mutations of the arginine vasopressin neurophysin II gene (AVP) on chromosome 20p13 have been described. Methods: Two Polish families with adFNDI were screened for mutations. Processing of wild-type (WT) and mutant AVP was monitored using immunocytochemical methods in stably transfected Neuro2A cells. AVP secretion into the cell culture supernatant was investigated with an enzyme immunoassay. Results: In the first family a heterozygous p.G96D mutation was identified. Some patients additionally carried a novel heterozygous mutation p.A159T. The second family presented with a heterozygous mutation p.C98G. Confocal laser microscopy unveiled accumulation of p.G96D and p.C98G prohormones in the cellular bodies, whereas WT and p.A159T prohormones and/or processed products were located in the tips of cellular processes. Reduced levels of AVP in supernatant culture medium of p.G96D and p.C98G transfected cells in comparison to p.A159T and WT cells were found. Conclusions: We conclude that the p.G96D and p.C98G mutations cause adFNDI in the two reported families. The sequence variant p.A159T does not seem to have disease-causing effects
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Background: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease with symptoms of polydipsia, polyuria and dehydration caused by arginine vasopressin deficiency. Disease onset is within infancy or adolescence. A variety of disease-causing mutations of the arginine vasopressin neurophysin II gene (AVP) on chromosome 20p13 have been described. Methods: Two Polish families with adFNDI were screened for mutations. Processing of wild-type (WT) and mutant AVP was monitored using immunocytochemical methods in stably transfected Neuro2A cells. AVP secretion into the cell culture supernatant was investigated with an enzyme immunoassay. Results: In the first family a heterozygous p.G96D mutation was identified. Some patients additionally carried a novel heterozygous mutation p.A159T. The second family presented with a heterozygous mutation p.C98G. Confocal laser microscopy unveiled accumulation of p.G96D and p.C98G prohormones in the cellular bodies, whereas WT and p.A159T prohormones and/or processed products were located in the tips of cellular processes. Reduced levels of AVP in supernatant culture medium of p.G96D and p.C98G transfected cells in comparison to p.A159T and WT cells were found. Conclusions: We conclude that the p.G96D and p.C98G mutations cause adFNDI in the two reported families. The sequence variant p.A159T does not seem to have disease-causing effects.
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Familial risk and environmental stress promote the development of alcohol dependence. We investigated whether a positive family history of alcoholism affects the neuroendocrine response to a standardized laboratory stress test in healthy subjects without alcohol use disorders. Twenty-four high-risk subjects with a paternal history of alcoholism (PHA) and 16 family history negative (FHN) controls were evaluated. Psychosocial stress was induced by having subjects deliver a 5-min speech and mental arithmetics in front of an audience on separate days, after drinking either placebo or ethanol (0.6 g/kg) in a randomized sequence. Adrenocorticotropin (ACTH) was measured in 10 plasma samples covering up to 75 min after the stress test. Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and at 75 min after stress onset. The stress test induced a phasic increase in ACTH secretion. At the time of maximum ACTH, AVP was significantly increased in relation to baseline. Compared to placebo, alcohol administration significantly attenuated maximum ACTH concentration in PHA but not FHN subjects, and decreased AVP measured in the same samples in PHA but not FHN subjects. We conclude that activation of the hypothalamic–pituitary–adrenal system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. Secretion of both ACTH and AVP suggest that alcohol attenuates the stress response selectively in PHA but not FHN subjects. This might imply some short-term positive alcohol effect in sons of alcoholics, but also constitute a mechanism by which their risk to develop alcohol use disorders is increased.

Familial risk and environmental stress promote the development of alcohol dependence. We investigated whether a positive family history of alcoholism affects the neuroendocrine response to a standardized laboratory stress test in healthy subjects without alcohol use disorders. Twenty-four high-risk subjects with a paternal history of alcoholism (PHA) and 16 family history negative (FHN) controls were evaluated. Psychosocial stress was induced by having subjects deliver a 5-min speech and mental arithmetics in front of an audience on separate days, after drinking either placebo or ethanol (0.6 g/kg) in a randomized sequence. Adrenocorticotropin (ACTH) was measured in 10 plasma samples covering up to 75 min after the stress test. Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and at 75 min after stress onset. The stress test induced a phasic increase in ACTH secretion. At the time of maximum ACTH, AVP was significantly increased in relation to baseline. Compared to placebo, alcohol administration significantly attenuated maximum ACTH concentration in PHA but not FHN subjects, and decreased AVP measured in the same samples in PHA but not FHN subjects. We conclude that activation of the hypothalamic–pituitary–adrenal system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. Secretion of both ACTH and AVP suggest that alcohol attenuates the stress response selectively in PHA but not FHN subjects. This might imply some short-term positive alcohol effect in sons of alcoholics, but also constitute a mechanism by which their risk to develop alcohol use disorders is increased.

Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base. O retorno da circulação espontânea ocorreu em 57% dos animais no grupo placebo (4 de 7) e 100% nos demais grupos (p = 0,002). A ! sobrevida em 1 hora foi de 57% no grupo placebo, 71,4% no grupo epinefrina, 90,5% no grupo terlipressina e de 100% nos demais grupos. Comparado com o grupo epinefrina, o grupo terlipressina teve maiores valores de PAM no T10 (164 vs 111 mmHg; p = 0,02), T20 (157 vs 97 mmHg; p < 0,0001), T30 (140 vs 67 mmHg; p < 0,0001), T45 (117 vs 67 mmHg; p = 0,002) e T60 (98 vs 62 mmHg; p = 0,026). O lactato arterial no grupo naloxona foi significativamente menor quando comparado ao grupo epinefrina, no T11 (5,15 vs 8,82 mmol/L), T31 (2,57 vs 5,24 mmol/L) e T59 (2,1 vs 4,1 mmol/L)[p = 0,002]. Ao longo da 1a hora pós-PCR, o grupo naloxona apresentou o melhor perfil do excesso de bases (-7,78 mmol/L) quando comparado ao grupo epinefrina (-12,78 mmol/L; p = 0,014) e ao grupo terlipressina (-11,31 mmol/L; p = 0,024). Conclusões: Neste modelo de PCR induzida por hipóxia em ratos, terlipressina e naloxona foram eficazes como vasopressores na RCP e apresentaram melhor perfil metabólico que a epinefrina. A terlipressina resultou em uma maior estabilidade hemodinâmica na 1a hora pós-PCR comparada com a epinefrina ou a vasopressina. Os efeitos metabólicos favoráveis da naloxona não são explicados pelos valores da PAM
Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo group and in 100% in the ! other groups (P=0.002). One-hour survival was 57% in the placebo group, 71.4% in the epinephrine group, 90.5% in the terlipressin and 100% in the naloxone group. Compared with the epinephrine group, the terlipressin groups had a significantly higher MAP at the T10 (164 x 111 mmHg; P=0.02), T20 (157 x 97 mmHg; P<0.0001), T30 (140 x 67 mmHg; P=0.0001), T45 (117 x 67 mmHg; P=0.002) and T60 (98 x 62 mmHg; P= 0.026). The blood lactate in naloxone group was significantly lower when compared to epinephrine group in the T11 (5.15 x 8.82 mmol/L), T31 (2.57 x 5.24 mmol/L) and T59 (2.1 x 4.1)[P=0.002]. Along the first hour after cardiac arrest, the naloxone group showed the best profile of base excess (- 7.78 mmol/L) when compared to epinephrine (-12.78 mmol/L, P= 0.014) and terlipressin group (-11.31 mmol/L, P=0.024). Conclusions: In this model of CA induced by hypoxia in rats, terlipressin and naloxone were effective as vasopressors in resuscitation and had better metabolic profile compared to epinephrine. Terlipressin resulted in higher hemodynamic stability in the first hour after CA and significantly better than epinephrine or vasopressin. The favorable metabolic effects of naloxone are not explained by the values of MAP

Thesis (Ph. D.)--Georgia State University, 2009.
Title from file title page. Chun Jiang, committee chair; Walter William Walthall, Delon W. Barfuss, Deborah Baro, committee members. Description based on contents viewed July 28, 2009. Includes bibliographical references. (p. 121-143)

Diabetes insipidus (DI) is associated with defects that involve the secretion and the action of hormone arginine vasopressin (AVP) resulting in the excretion of abnormally large volumes of diluted urine. The most common defect that results in disease development is the deficient secretion of the hormone AVP and the disease is referred to as central or neurohypophyseal DI. The AVP hormone is synthesized in magnocellular neurons, that originate in the supraoptic and paraventricular nuclei of the hypothalamus and are projected to neurohypophysis, and the destruction of these neurons leads to a deficiency of AVP hormone, resulting in neurohypophyseal DI. The familial form of disease represents 1% of all causes of neurohypophyseal DI and the main points of the disease are: it is associated with mutations in one allele of the AVP gene, and it is caused by postnatal development of deficient AVP secretion, proposed to result from selective degeneration of the magnocellular neurons. The aims of this thesis are: to review AVP mutations described in the scientific literature, to expand the spectrum of mutations through the analysis of additional patients with DI and to characterize the functional consequences of identified novel AVP mutations. To achieve these aims a bibliographic research was developed; genetic studies were performed to amplify and to sequence the three exons of the AVP gene in 9 patients; an expression vector containing the desired mutations was constructed by subcloning, site-directed mutagenesis and enzymatic digestion; and the functional studies were initialized by optimization of transfection and immunocytochemistry assays for WT AVP cDNA expression vector. Three mutations were identified: c.154T>C, c.289C>G and c.343G>T. The first two mutations are novel and the last mutation is already described in the scientific literature. The AVP cDNA from the expression vector was subcloned in the pVAX/lacZ vector and the mutations were inserted in the AVP cDNA by site-directed mutagenesis and enzymatic digestion. The mutated AVP cDNAs were sequenced and have been prepared to be inserted in the expression vector. The transfection and immunocytochemistry protocols have been optimized for WT AVP cDNA expression vector. This study allowed the increase in the number of mutations from 70 to 72 different mutations, although further work is necessary in order to understand the molecular mechanisms responsible for the development of the disease and to give help and information to patients affected with this disease.
A diabetes insípida (DI) é uma doença rara, caracterizada principalmente pela excreção de elevados volumes de urina na forma diluída podendo, entre várias causas possíveis, ter origem num defeito genético. O desenvolvimento da doença pode dever-se a quatro causas possíveis. A mais comum deve-se a uma deficiência na secreção da hormona antidiurética arginina vasopressina (AVP), sendo referida como DI central ou neurohipofisária. Outra possível causa da doença deve-se a uma insensibilidade, por parte das células renais, aos efeitos da AVP, sendo neste caso designada como DI nefrogénica. A DI pode também dever-se a uma excessiva ingestão de líquidos, que conduz à supressão da libertação da hormona AVP, sendo referida como polidipsia primária. Por fim, um aumento do metabolismo da hormona AVP durante a gravidez pode também ser uma causa da doença, designada por DI gestacional. A hormona AVP é sintetizada nos neurónios magnocelulares. Estes têm origem no núcleo supra-óptico e para-ventricular do hipotálamo e os seus prolongamentos terminam na neurohipófise. A destruição destes neurónios resulta numa deficiência na produção da hormona, conduzindo à DI central. Esta destruição pode ter inúmeras causas, incluindo acidentes, cirurgias, doenças autoimunes, entre outras. Contudo, a doença também apresenta uma base familiar, correspondendo a 1% de todas as causas de DI central. A DI central apresenta sintomas persistentes de poliúria, polidipsia e sede, que geralmente se começam a manifestar vários meses ou anos após o nascimento. A DI central familiar apresenta duas características principais: está associada a mutações num único alelo do gene que codifica a hormona (gene AVP), apresentando assim uma transmissão autossómica dominante; e é causada por uma deficiência progressiva pós-natal na secreção da hormona AVP, que se pensa resultar da degeneração seletiva dos neurónios magnocelulares. O gene AVP é composto por 3 mil pares de bases e encontra-se localizado no braço curto do cromossoma 20. Este gene contém três exões que codificam para o péptido sinalizador, para a hormona AVP, para a neurofisina II (transportador da hormona) e ainda para um glicopéptido, conhecido como copeptina. Após sintetizados, a hormona, a neurofisina II e o glicopéptido são armazenados em vesiculas secretoras, nos terminais axonais dos neurónios, e são libertados após a ocorrência de estímulos. Após a entrada na corrente sanguínea, a hormona vai atuar a nível das células renais de modo a aumentar a sua permeabilidade para as moléculas de água, favorecendo assim a absorção de água no rim. Até à data do início deste trabalho, a doença estava associada a 70 mutações diferentes no gene AVP localizadas ao longo de todo o precursor proteico. Pensa-se que estas mutações são a causa da doença uma vez que interferem na estabilidade da cadeia de aminoácidos, alterando a sua estrutura primária. Teoricamente, mutações que afetem a conformação de proteínas secretoras resultam no desenvolvimento de patologias devido ao seu impacto na função da proteína não conseguindo alcançar o seu destino, ficando retidas no reticulo endoplasmático. Contudo, a razão dos precursores AVP mutados serem tóxicos para os neurónios produtores de AVP está ainda por esclarecer. Existem, até ao momento, três teorias que tentam explicar o mecanismo da doença. O mecanismo não tóxico defende que há uma expressão simultânea dos precursores “wild-type” e dos precursores mutados resultando numa associação de ambos. Assim, o precursor “wildtype” é alterado, uma vez que ambos ficam retidos no reticulo endoplasmático. Contudo, este mecanismo não explica a morte dos neurónios magnocelulares. O mecanismo tóxico defende que a constante acumulação de precursores com conformações alteradas pode interferir com a produção de proteínas essenciais à sobrevivência celular, resultando assim na morte neuronal. Recentemente, um novo mecanismo foi proposto para explicar a patogénese da doença. Observou-se a formação de vesiculas autofágicas, após acumulação de precursores mutados, que resultam na destruição dos retículos endoplasmáticos danificados, juntamente com os agregados proteicos. Durante este processo, se as células forem expostas a insultos metabólicos e ambientais, pode ocorrer apoptose dependente de autofagia, resultando na destruição dos neurónios magnocelulares. A DI central familiar apresenta uma natureza benigna, contudo é uma doença que apresenta uma intensa pesquiza em torno dos seus mecanismos moleculares uma vez que se trata de um modelo de interesse para o estudo de doenças neuro-endócrinas e de transmissões autossómica dominante. O presente estudo tem por objetivos fazer uma revisão das mutações descritas na literatura científica para o gene AVP, aumentar o número de mutações descritas com a análise de novos pacientes diagnosticados com DI central familiar e caracterizar as consequências funcionais das novas mutações identificadas. Para alcançar os objetivos descritos, utilizou-se a seguinte metodologia: a revisão de todas as mutações descritas até à data, através de pesquisa bibliográfica de artigos científicos; realização de estudos genéticos, baseados na amplificação por PCR e na posterior sequenciação dos três exões do gene AVP de 9 pacientes diagnosticados com DI central familiar; inserção das novas mutações num vector de expressão contendo o cDNA do gene AVP, através de técnicas de clonagem, digestão enzimática e mutagénese dirigida; e finalmente a realização de estudos funcionais, por otimização das técnicas de transfecção e imunocitoquímica com o vector de expressão AVP “wild-type”. Os resultados obtidos mostraram que as 3 famílias apresentam mutações no gene AVP. O paciente III-1, da família A, apresenta a alteração de uma timina para uma citosina na posição 154 do cDNA (c.154T>C) que origina a substituição de uma cisteína por arginina na posição 52 da proteína (p.C52R). O paciente II-1, da família B, apresenta uma alteração de citosina para guanina na posição 289 do cDNA (c.289C>G) que resulta na substituição de uma arginina por glicina, na posição 97 da proteína. O paciente II-4 da família C apresenta a alteração de uma guanina para uma timina na posição 343 do cDNA (c.343G>T) que resulta na substituição de um ácido glutâmico por um codão de terminação na posição 115 da proteína. As três mutações estão em heterozigotia e as duas mutações encontradas no exão 2 correspondem a mutações novas, enquanto a mutação presente no exão 3 já se encontra descrita na literatura. Um vector de expressão contendo o cDNA do gene AVP (pRc/RSV-AVP), foi-nos gentilmente oferecido por investigadores da área. O cDNA do gene AVP contido no vector de expressão (pRc/RSV-AVP) foi sub-clonado no vector pVAX/lacZ e, através de mutagénese dirigida, as mutações desejadas (c.154T>C e c.289C>G) foram introduzidas no cDNA. Assim, o cDNA com as mutações está pronto a ser inserido no plasmídeo de expressão. Os ensaios de transfecção e imunocitoquímica foram otimizados para o vector de expressão “wild-type”, uma vez que foi observada marcação para a neurofisina II nos prolongamentos dos neurónios após transfecção de uma linha celular neuronal (N2A) e marcação com anticorpos específicos. Com este estudo, o número de mutações descritas para o gene AVP aumentou de 70 para 72 e mais três famílias fazem parte do número total de famílias estudadas com DI central familiar. É importante continuar o desenvolvimento de estudos funcionais, de modo a obter respostas sobre os mecanismos moleculares responsáveis pelo desenvolvimento da doença uma vez que estas serão importantes não só para a DI central familiar, mas também para o esclarecimento de outras doenças que apresentem mecanismos moleculares semelhantes.

Yes
The antidiuretic hormone arginine vasopressin (AVP) regulates water homeostasis, blood pressure and a range of stress responses. It is synthesized in the hypothalamus and released from the posterior pituitary into the general circulation upon a range of stimuli. While the mechanisms leading to AVP secretion have been widely investigated, the molecular mechanisms regulating AVP gene expression are mostly unclear. Here we investigated the neurotransmitters and signal transduction pathways that activate AVP gene expression in the paraventricular nucleus (PVN) of the rat using acute brain slices and quantitative real-time PCR. We show that stimulation with l-glutamate robustly induced AVP gene expression in acute hypothalamic brain slices containing the PVN. More specifically, we show that AVP transcription was stimulated by NMDA. Using pharmacological treatments, our data further reveal that the activation of ERK1/2 (PD184352), CaMKII (KN-62) and PI3K (LY294002; 740 Y-P) is involved in the NMDA-induced AVP gene expression in the PVN. Together, this study identifies NMDA-mediated cell signalling pathways that regulate AVP gene expression in the rat PVN.
Supported by a generous donation from Jonathan Feuer.