Regulation of Na(+)/H(+) exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells

Carraro-Lacroix LR, Malnic G, Girardi AC. Regulation of Na(+)/H(+) exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol 297: F1647-F1655, 2009. First published September 23, 2009; doi:10.1152/ajprenal.00082.2009.-The gut incretin hormone glucagon-like peptide 1 (GLP-1) is released in response to ingested nutrients and enhances insulin secretion. In addition to its insulinotropic properties, GLP-1 has been shown to have natriuretic actions paralleled by a diminished proton secretion. We therefore studied the role of the GLP-1 receptor agonist exendin-4 in modulating the activity of Na(+)/H(+) exchanger NHE3 in LLC-PK(1) cells. We found that NHE3-mediated Na(+)-dependent intracellular pH (pH(i)) recovery decreased similar to 50% after 30-min treatment with 1 nM exendin-4. Pharmacological inhibitors and cAMP analogs that selectively activate protein kinase A (PKA) or the exchange protein directly activated by cAMP (EPAC) demonstrated that regulation of NHE3 activity by exendin-4 requires activation of both cAMP downstream effectors. This conclusion was based on the following observations: 1) the PKA antagonist H-89 completely prevented the effect of the PKA activator but only partially blocked the exendin-4-induced NHE3 inhibition; 2) the MEK1/2 inhibitor U-0126 abolished the effect of the EPAC activator but only diminished the exendin-4-induced NHE3 inhibition; 3) combination of H-89 and U-0126 fully prevented the effect of exendin-4 on NHE3; 4) no additive effect in the inhibition of NHE3 activity was observed when exendin-4, PKA, and EPAC activators were used together. Mechanistically, the inhibitory effect of exendin-4 on pHi recovery was associated with an increase of NHE3 phosphorylation. Conversely, this inhibition took place without changes in the surface expression of the transporter. We conclude that GLP-1 receptor agonists modulate sodium homeostasis in the kidney, most likely by affecting NHE3 activity.

Functional Expression of Chemoreceptors with the Help of a Guanine Nucleotide Exchange Factor

Odorant receptors and other chemoreceptors are usually poorly expressed in the plasma membrane of heterologous cells. A key point of regulation in G protein-mediated signaling is the interconversion between the active GTP-bound and inactive GDP-bound states of the G alpha subunit, which regulatory proteins, such as guanine nucleotide exchange factors (GEFs), can control. GEFs stimulate formation of the GTP-bound state of G alpha and therefore are considered to work as positive regulators of G protein-coupled receptor signaling. Ric-8B, a GEF that is specifically expressed in olfactory sensory neurons, promotes functional expression of odorant receptors in HEK293T cells because it amplifies the initially low receptor signaling through G alpha olf. This same strategy could be used to functionally express other types of chemoreceptors.

Are price limits on futures markets that cool? evidence from the brazilian merchantile & futures exchange

This paper investigates the impact of price limits on the Brazil- ian future markets using high frequency data. The aim is to identify whether there is a cool-off or a magnet effect. For that purpose, we examine a tick-by-tick data set that includes all contracts on the São Paulo stock index futures traded on the Brazilian Mercantile and Futures Exchange from January 1997 to December 1999. Our main finding is that price limits drive back prices as they approach the lower limit. There is a strong cool-off effect of the lower limit on the conditional mean, whereas the upper limit seems to entail a weak magnet effect on the conditional variance. We then build a trading strategy that accounts for the cool-off effect so as to demonstrate that the latter has not only statistical, but also economic signifi- cance. The resulting Sharpe ratio indeed is way superior to the buy-and-hold benchmarks we consider.

Are price limits on futures markets that cool?: evidence from the Brazilian Mercantile and Futures Exchange

This paper investigates the impact of price limits on the Brazilian futures markets using high frequency data. The aim is to identify whether there is a cool-off or a magnet effect. For that purpose, we examine a tick-by-tick data set that includes all contracts on the S˜ao Paulo stock index futures traded on the Brazilian Mercantile and Futures Exchange from January 1997 to December 1999. The results indicate that the conditional mean features a floor cool-off effect, whereas the conditional variance significantly increases as the price approaches the upper limit. We then build a trading strategy that accounts for the cool-off effect in the conditional mean so as to demonstrate that the latter has not only statistical, but also economic significance. The in-sample Sharpe ratio indeed is way superior to the buy-and-hold benchmarks we consider, whereas out-of-sample results evince similar performances.

A estrutura de regulação dos mercados futuros no Brasil e o uso de modelos estatísticos de precificação na atividade de supervisão dos órgãos reguladores

Esta dissertação procurou identificar as diretrizes de supervisão dos mercados futuros no Brasil frente às práticas de regulação utilizadas em outros países do mundo, basicamente aqueles cujas economias e mercados são maiores do que o brasileiro, em volume de contratos negociados. O desenvolvimento do tema se deu de maneira a estimular o uso de tais práticas na estrutura local de supervisão, com vistas a uma melhoria da atividade dos órgãos reguladores e ao crescimento do mercado de capitais brasileiro. Dentre as referidas práticas, destacou-se a utilização de modelos estatísticos de precificação dos contratos negociados no sentido de balizar a atuação dos departamentos de fiscalização na investigação de condições artificiais de mercado. A abordagem desses modelos abrangeu desde a definição de conceitos fundamentais até a apresentação de um estudo de caso com opções sobre ações, passando pela caracterização dos principais modelos e formas de calcular a volatilidade no preço desses títulos. Os resultados de pesquisa foram relacionados às origens legais e ao desenvolvimento econômico recente do Brasil, que levaram à sofisticação dos mecanismos de financiamento do mercado de capitais nacional, não se limitando ao simples apontamento dos pontos fracos da estrutura local de supervisão. Finalmente, a pesquisa evoluiu para as necessidades práticas da atividade de supervisão a serem atendidas pelo regulador, segundo as características operacionais dos principais mercados, a fim de que a bolsa de futuros brasileira reforce sua posição competitiva no cenário mundial.

A estrutura de regulação dos mercados futuros no Brasil e o uso de modelos estatísticos de precificação, na atividade de supervisão dos órgãos reguladores.

Esta dissertação procurou identificar as diretrizes de supervisão dos mercados futuros no Brasil frente às práticas de regulação utilizadas em outros países do mundo, basicamente aqueles cujas economias e mercados são maiores do que o brasileiro, em volume de contratos negociados. O desenvolvimento do tema se deu de maneira a estimular o uso de tais práticas na estrutura local de supervisão, com vistas a uma melhoria da atividade dos órgãos reguladores e ao crescimento do mercado de capitais brasileiro. Dentre as referidas práticas, destacou-se a utilização de modelos estatísticos de precificação dos contratos negociados no sentido de balizar a atuação dos departamentos de fiscalização na investigação de condições artificiais de mercado. A abordagem desses modelos abrangeu desde a definição de conceitos fundamentais até a apresentação de um estudo de caso com opções sobre ações, passando pela caracterização dos principais modelos e formas de calcular a volatilidade no preço desses títulos. Os resultados de pesquisa foram relacionados às origens legais e ao desenvolvimento econômico recente do Brasil, que levaram à sofisticação dos mecanismos de financiamento do mercado de capitais nacional, não se limitando ao simples apontamento dos pontos fracos da estrutura local de supervisão. Finalmente, a pesquisa evoluiu para as necessidades práticas da atividade de supervisão a serem atendidas pelo regulador, segundo as características operacionais dos principais mercados, a fim de que a bolsa de futuros brasileira reforce sua posição competitiva no cenário mundial.

Essays on regulation and risk

In this thesis, we investigate some aspects of the interplay between economic regulation and the risk of the regulated firm. In the first chapter, the main goal is to understand the implications a mainstream regulatory model (Laffont and Tirole, 1993) have on the systematic risk of the firm. We generalize the model in order to incorporate aggregate risk, and find that the optimal regulatory contract must be severely constrained in order to reproduce real-world systematic risk levels. We also consider the optimal profit-sharing mechanism, with an endogenous sharing rate, to explore the relationship between contract power and beta. We find results compatible with the available evidence that high-powered regimes impose more risk to the firm. In the second chapter, a joint work with Daniel Lima from the University of California, San Diego (UCSD), we start from the observation that regulated firms are subject to some regulatory practices that potentially affect the symmetry of the distribution of their future profits. If these practices are anticipated by investors in the stock market, the pattern of asymmetry in the empirical distribution of stock returns may differ among regulated and non-regulated companies. We review some recently proposed asymmetry measures that are robust to the empirical regularities of return data and use them to investigate whether there are meaningful differences in the distribution of asymmetry between these two groups of companies. In the third and last chapter, three different approaches to the capital asset pricing model of Kraus and Litzenberger (1976) are tested with recent Brazilian data and estimated using the generalized method of moments (GMM) as a unifying procedure. We find that ex-post stock returns generally exhibit statistically significant coskewness with the market portfolio, and hence are sensitive to squared market returns. However, while the theoretical ground for the preference for skewness is well established and fairly intuitive, we did not find supporting evidence that investors require a premium for supporting this risk factor in Brazil.

Essays on economic regulation

It is known that stock prices of public listed regulated companies react to price revisions by the regulator, and that the information conveyed by this price reaction might be used by the regulator on the contract design. This paper builds on Laffont and Tirole's (1986) regulation model with observable costs to better understand the effects the inclusion of the stock market can have on the regulator-regulated firm relationship. Our numerical simulations show that the inclusion of the market induce more powerful incentive schemes, with higher cost-reducing efforts, smaller informational rent by the firms and higher overall social welfare. In particular, we find that when the regulator is committed, the presence of short-term investors can make the first-best contract feasible, and that in the non-commitment case the market affects the firm's strategy by making it reveal more information about its cost than it normally would.

Essays on incentives, procurement and regulation

Esta tese é composta de três artigos. No primeiro artigo, "Simple Contracts under Simultaneous Adverse Selection and Moral Hazard", é considerado um problema de principal-agente sob a presença simultânea dos problemas de risco moral e seleção adversa, em que a dimensão de seleção adversa se dá sobre as distribuições de probabilidade condicionais as ações do agente. No segundo artigo, "Public-Private Partnerships in the Presence of Adverse Selection" é analisada a otimalidade de parcerias público-privadas sob a presença de seleção adversa. No terceiro artigo, "Regulation Under Stock Market Information Disclosure", por sua vez, é considerado o problema da regulação de firmas de capital aberto, onde as firmas possuem incentivos para mandar sinais opostos para o regulador e o mercado.

Consumption-Wealth Ratio and Expected Stock Returns: Evidence from Panel Data on G7 Countries

Using the theoretical framework of Lettau and Ludvigson (2001), we perform an empirical investigation on how widespread is the predictability of cay {a modi ed consumption-wealth ratio { once we consider a set of important countries from a global perspective. We chose to work with the set of G7 countries, which represent more than 64% of net global wealth and 46% of global GDP at market exchange rates. We evaluate the forecasting performance of cay using a panel-data approach, since applying cointegration and other time-series techniques is now standard practice in the panel-data literature. Hence, we generalize Lettau and Ludvigson's tests for a panel of important countries. We employ macroeconomic and nancial quarterly data for the group of G7 countries, forming an unbalanced panel. For most countries, data is available from the early 1990s until 2014Q1, but for the U.S. economy it is available from 1981Q1 through 2014Q1. Results of an exhaustive empirical investigation are overwhelmingly in favor of the predictive power of cay in forecasting future stock returns and excess returns.

Exchange rate management techniques

This briefing note addresses the question: What revisions of financial regulation and financial governance in Brazil are necessary to support Brazilian development? What’s in place and what’s missing? The focus here is a dimension of financial regulation and governance: the regulation of capital flows and of exchange rate operations. The arguments are organized in the following manner. In the next section, we summarize the impacts of th crisis on the emerging-market economies and on the regulation of the international monetary and financial system. The third section discusses the post-crisis dilemmas faced by these economies. Finally, the fourth section presents some policy recommendations for Brazil.

Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses

P>Reasons for performing study:Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl- and HCO(3)- exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses.Objectives:To determine the effects of Carbonic anhydrase inhibition on CO(2) output and ionic exchange between erythrocytes and plasma and their influence on acid-base balance in the pulmonary circulation (across the lung) in exercising horses with and without CA inhibition.Methods:Six horses were exercised to exhaustion on a treadmill without (Con) and with CA inhibition (AczTr). CA inhibition was achieved with administration of acetazolamide (10 mg/kg bwt t.i.d. for 3 days and 30 mg/kg bwt before exercise). Arterial, mixed venous blood and CO(2) output were sampled at rest and during exercise. An integrated physicochemical systems approach was used to describe acid base changes.Results:AczTr decreased the duration of exercise by 45% (P < 0.0001). During the transition from rest to exercise CO(2) output was lower in AczTr (P < 0.0001). Arterial PCO(2) (P < 0.0001; mean +/- s.e. 71 +/- 2 mmHg AczTr, 46 +/- 2 mmHg Con) was higher, whereas hydrogen ion (P = 0.01; 12.8 +/- 0.6 nEq/l AczTr, 15.5 +/- 0.6 nEq/l Con) and bicarbonate (P = 0.007; 5.5 +/- 0.7 mEq/l AczTr, 10.1 +/- 1.3 mEq/l Con) differences across the lung were lower in AczTr compared to Con. No difference was observed in weak electrolytes across the lung. Strong ion difference across the lung was lower in AczTr (P = 0.0003; 4.9 +/- 0.8 mEq AczTr, 7.5 +/- 1.2 mEq Con), which was affected by strong ion changes across the lung with exception of lactate.Conclusions:CO(2) and chloride changes in erythrocytes across the lung seem to be the major contributors to acid-base and ions balance in pulmonary circulation in exercising horses.

Developing countries' anti-cyclical policies in a globalized world

Includes bibliography

Developing countries' anti-cyclical policies in a globalized world

Includes bibliography

Financial crisis and national policy issues: an overview

Includes bibliography