Mishell Ramirez

Reducing angiotensin II (Ang II) production via angiotensin-converting enzyme (ACE) inhibitors is a key approach for the treatment of hypertension. However, these inhibitors may also affect other enzymes, such as angiotensinases and vasopressinase, responsible for the metabolism of other peptides also involved in blood pressure control, such as Ang...

If it is well-known that the renin-angiotensin system (RAS) participates in the regulation of blood pressure (BP) through the binding of Ang II to the AT1 receptor, other multiple factors of this and additional systems interact together to maintain the BP in physiologic conditions. The imbalance between these factors will lead to alterations of BP....

In order to study the interaction between the renin-angiotensin system (RAS) and nitric oxide (NO), we analyzed the activity of aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP), and cystinylaminopeptidase (CysAP) enzymes involved in the RAS cascade, in the hypothalamus, and plasma of normotensive adult male rats after the inhibition of NO prod...

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by a progressive motor disorder, but frequently is accompanied by autonomic symptoms such as hypotension. Together with the decrease of dopamine, significant decreases in aminopeptidase activities have been reported in PD brains. However, up to date there are no stud...

Thyroid disorders affect renal function, which involves changes in local renin angiotensin system (RAS). Angiotensin peptide levels in the tissue are regulated by the activity of several aminopeptidases (AP) known as angiotensinases. The nature and consequences of the thyroid-induced RAS changes are not completely understood. We investigated the re...

There are important asymmetries in brain functions such as emotional processing and stress response in humans and animals. Knowledge of the bilateral distribution of brain neurotransmitters is important to appropriately understand its functions. Some peptides such as those included in the renin-angiotensin system (RAS) and cholecystokinin (CCK) are...

A local renin-angiotensin system (RAS) that may be involved in their regulatory functions has been identified in hypothalamus and pituitary. Altered thyroid status induces modifications in the secretory function of hypothalamus and pituitary. However, few studies have analyzed the role of the RAS in hypothalamus and, to our knowledge, there is no d...

Several studies have addressed the interaction between fatty acids and lipids with central nervous system peptides. Because aminopeptidases (AP) are involved in the regulation of neuropeptides, this work studies several AP expressed in cultured astroglia, after exogenous addition of oleic and linoleic fatty acids and cholesterol to the culture medi...

Aminopeptidases (APs) are important regulators of peptides directly involved in water homeostasis such as angiotensins (Ang) and vasopressin (AVP). Sex differences in water balance and differences in the effects of gonadal steroids on osmotic stimulation of vasopressin secretion have been reported. Since sex steroids may be involved, the gonadotrop...

Oxytocin (OT), locally synthesized in the testis, is involved in androgen biosynthesis. The use of polyunsaturated fatty acids (e.g., fish oil) in the diet may improve the fertilizing ability in mammals. Cystinyl aminopeptidase (oxytocinase) activity plays a major role regulating the functional status of OT. Sex steroids and the type of the fatty a...

Given that the existence of a local renin-angiotensin system (RAS) in the pituitary and its participation in the regulation of blood pressure and other biological functions are widely accepted, the aim of this work is to analyze the influence of dietary cholesterol on the activity of the enzymes involved in the metabolism of the effector peptides o...

Alterations in thyroid function imply important changes in cardiovascular response, in which are also involved modifications in the renin angiotensin system (SRA) and other vasoactive peptides. Aminopeptidase (AP) activity, through the control of thyrotrophin releasing hormone, the SRA and other vasoactive peptides such as vasopressin, plays an imp...

Pyroglutamyl-ended forms of amyloid-beta-peptide are present in senile plaques in some individuals with Alzheimer type dementia. Single oral administration of the acetylcholinesterase inhibitor SDZ ENA 713 (rivastigmine (+)-(S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methylphenylcarbamate hydrogen tartrate) increases basal and K(+)-stimulated pyrrolid...

Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase widely distributed in fluid and tissues which hydrolyses biological active peptides including thyrotropin releasing hormone (TRH). OBJECTIVES. The aim of present work is to study the influence of estradiol on soluble and membrane bound pGluAP activity in the frontal cortex of female mice. S...

It is well known the depressor effect of alcohol on several inhibitory nervous centres. This can be due to the inhibition that induces in the release of different type of neurotransmitters, and because alcohol can increase the membrane fluidity and changes the function of proteins inserted in the membrane. Several aminopeptidases (AP) have been des...

To evaluate the influence of light and darkness on brain pyroglutamyl-peptidase I (pGluPI) activity, four experimental groups of rats were compared at the same time-point (10.00 h). Two groups were designed with a standard 12-12 h light-dark cycle: In group A, the lights were on from 7.00 h to 19.00 h, and the experiment was done under light condit...

Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase widely distributed in fluid and tissues, which hydrolyses biological active peptides including thyrotropin-releasing-hormone (TRH). In the last years, different endocrine and extraendocrine functions have been attributed to TRH. The aim of present work is to study the influence of high diet...

The intake of mono- and polyunsaturated fatty acids has been associated with a minor risk of cardiovascular diseases including hypertension. Changes in levels of fatty acids may also modify the cell activity and may be related with alterations in different regulatory processes. Aminopeptidases are zinc-metalloenzymes which metabolise circulating pe...

Objectives. The aim of this work is to study the existence of a relationship between high dietary cholesterol and hypertension in the central nervous system, so we analyzed the changes on angiotensinase activity (Aspartyl- and Glutamyl-aminopeptidase, Asp- and GluAP) in the frontal cortex of male and female mice fed with an enriched cholesterol die...

Objectives. Given that the existence of a local renin-angiotensin system in the central nervous system and its participation in the regulation of blood pressure and other biological functions are widely accepted, the aim of this work is to analyze the influence of estradiol on the enzymes involved in the metabolism of angiotensin II: Aspartyl and G...

We studied the in vitro effects of ethanol (25, 50 and 100 mM) on pyroglutamyl aminopeptidase activity (pGluAP), which has been reported as thyrotrophin-releasing-hormone-degrading activity. pGluAP was measured in presence or absence of calcium, under basal and K(+)-stimulated conditions, in synaptosomes and their incubation supernatant, using pyro...

Thyrotrophin releasing hormone (TRH) has emerging in the last few years as a neuropeptide with important functions, not only as neurohormone into the hypothalamus-pituitary axis, but as neurotransmitter in several areas of the nervous system. Although little is known about its extra-endocrine functions, TRH has been related with several types of ps...

To evaluate the functional role of glutamyl and aspartyl aminopeptidases, their soluble and membrane-bound activities were measured simultaneously in several tissues of normal mice using arylamide derivatives as substrates. Although the soluble aspartyl aminopeptidase activity showed its highest levels in the testicle, the rest of the activities pr...

Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase which removes pyroglutamyl N-terminals residues from peptides and arylamidase derivatives. This activity is thought to be involved in the regulation of several physiological mechanisms on the central nervous system. pGluAP can modulate various susceptible endogenous substrates such as thyro...

Objective. One of the mechanisms responsible for neurodegenerative processes affecting te central nervous system is the hyperexcitabitily of amino acid neurotransmitters, particularly glutamic and aspartic acids. That excitatory amino acids act like strong endogenous toxins, which induce degeneration and neuron death. The activity of aminopeptidase...

Changes in fatty acid composition of membrane lipids induce modifications on the activity of several enzymes and membrane transporters. Glial cells possess aminopeptidases which are located in the plasma membranes. Aminopeptidases are generally zinc-metalloenzymes which hydrolyze peptide bonds near the N-terminal end of peptides and polypeptides. T...

Changes in fatty acid composition of membrane lipids induce modifications on the activity of several enzymes and membrane transporters, Glial cells possess aminopeptidases which are located in the plasma membranes. Aminopeptidases are generally zinc-metalloenzymes which hydrolyze peptide bonds near the N-terminal end of peptides and polypeptides. T...

Distribución tisular de actividades aminopeptidásicas en un modelo de hipertensión arterial 1. En el presente trabajo hemos estudiado, en un modelo de hipertensión de masa renal reducida, la distribución de diferentes actividades aminopeptidásicas que han sido involucradas en la patogenia de la hipertensión. Las actividades de la angiotensina A (gl...

Objective. High fat diets are associated with several types of vascular diseases. Several epidemiological studies have demonstrated that Mediterranean countries population suffer a lower percent of vascular diseases that North Europe or United States population. In Mediterranean countries, diet contents a high amount of monounsaturated fatty acids,...

Aminopeptidase activity (AP) has been implicated in the metabolism of renal and circulating vasoactive peptides. This activity is involved in the pathogenia of hypertension, essentially in spontaneously hypertensive rats. However, no other animal models, which develop hypertension by other different ways, have been used to study the possible role o...

Specific soluble and membrane-bound aspartyl-naphthylamide hydrolyzing activities were assayed in brain subcellular fractions from rat fetuses (19-20 days of gestation), and from 1-week-old and 1-, 5- and 24-month-old rats. Both enzymatic activities showed a heterogeneous distribution, with highest concentrations mainly in the microsomal fraction....

The subcellular distribution of soluble and membrane-bound Arg-beta-naphthylamide-hydrolyzing activities was studied in the left and right rat brain during development and aging. During development, the soluble activity was heterogeneous, whereas adult animals showed the highest activity in the synaptosomal fraction. However, except in fetuses, mem...

Aminopeptidase activities, assayed as arylamidase activities, were investigated in selected tissues of 1, 6, 12 and 24-month-old rats. The enzyme activities were found to have a heterogeneous distribution and age-related changes were observed. The highest levels of soluble arginyl-aminopeptidase activity were detected in brain homogenate at all the...

Aminopeptidase activities, assayed as arylamidase activities, were investigated in selected tissues of 1, 6, 12 and 24-month-old rats. The enzyme activities were found to have a heterogeneous distribution and age-related changes were observed. The highest levels of soluble arginyl-aminopeptidase activity were detected in brain homogenate at all the...

Soluble and membrane-bound aminopeptidase activities in 11 regions of the rat brain were assayed using L-Leucine-2-naphthylamide as a substrate. In addition, two metabolic enzymatic activities were compared: lactate dehydrogenase and aspartate aminotransferase. All enzymatic activities showed significant regional differences when the data were anal...

The levels of specific soluble aspartyl aminopeptidase activity were assayed in retina, occipital cortex, anterior pituitary, posterior pituitary, pineal gland and serum of adult male rats, using Asp-2-naphthylamide as substrate, in a 12:12 h light:dark cycle (7-19 h light). Significant diurnal variations appeared in retina, pineal gland, occipital...

Soluble and membrane-bound aminopeptidase activities in eleven regions of the rat brain were assayed using L-leucine-2-naphthylamide as a substrate. In addition, two metabolic enzymatic activities were compared: lactate dehydrogenase and aspartate aminotransferase. All enzymatic activities showed significant regional differences when the data were...

Provided that soluble aminopeptidases, the most abundant proteolytic enzymes found in brain, are involved in the metabolism of several neuropeptides, their activity could be a reflect of neuropeptide function. Therefore, in order to analyze their rate of participation, we have measured 4 soluble aminopeptidase activities: leucine aminopeptidase, ar...

Soluble Leu-beta-naphthylamide hydrolysing activity (arylamidase activity) was assayed in retina, superior cervical ganglia, several brain areas and serum of adult male rats, at different time points of a 12:12h light:dark cycle (from 7h to 19h light). The results demonstrated a left or right biased asymmetrical distribution of this activity depend...

The thyroliberin and luliberin contents exhibit a diurnal rhythm within the brain and an asymmetrical distribution of both neuropeptides has been demonstrated in the hypothalamus. Since they have been described as substrates of pyroglutamyl peptidase I, this activity was analysed in several rat brain regions and other structures, in order to invest...

The levels of soluble and membrane-bound aminopeptidase activities were assayed in subcellular fractions from young (1 month old) and adult (5 month old) left and right rat brains, using Leu-, Arg- and Asp-2-naphthylamide as substrates. Both soluble Leu- and Arg-aminopeptidase activities showed the highest levels in the synaptosomal fraction in the...

The subcellular distribution of soluble and membrane-bound leucyl- and arginyl-aminopeptidase activities were analyzed in one and five month old rat brains using Leu- and Arg-2-naphthylamide as substrates. Both soluble leucyl- and arginyl-aminopeptidase activities showed the highest levels in the synaptosomal fraction in the two groups of rats. The...

Research into the functional role of brain peptides is performed, in part, by studying peptidase enzymes which might be involved in the processing or inactivation of the brain peptides. Aminopeptidase activity has been proposed as a candidate for the regulation of the degradation of these peptides. In this paper, acid (Asp-) and basic (Arg-) aminop...

The levels of soluble and membrane-bound aminopeptidase activities were assayed in subcellular fractions from young (4 weeks old) and adult (20 weeks old) rat brains, using Asp-2-naphthylamide as substrate. The young rats showed the highest soluble and membrane-bound levels of activity in the microsomal fraction but no differences among fractions w...

Aminopeptidase activity has been assayed from both soluble and membrane bound fractions in eleven regions of the left and right hemispheres of the rat brain, using L-leucine-2-naphthylamide as substrate. Two other metabolic enzymes, lactate dehydrogenase and glutamate-oxalacetate aminotransferase activities were simultaneously determined in the sam...

Subcellular distribution of soluble and membrane-bound Leu-, Arg- and Asp-beta-naphthylamide hydrolysing activities (arylamidase activity) was studied from left and right rat brains, each including hemisphere, cerebellum and brain stem. Both soluble Leu- and Arg-beta-naphthylamide hydrolysing activities showed the highest levels in the synaptosomal...

Peptidase enzymes are involved in neuropeptide processing or degradation. In order to analyse a possible functional participation of these enzymes, arylamidase activity of several rat brain regions and serum was assayed in the soluble fraction during the estrous cycle using L-Lys- and L-Tyr-beta-naphthylamide as substrates. Significant differences...

A fluorometric method adapted to the determination of brain aminopeptidase activities has been developed in our laboratory. This method is based in the fluorescence produced by 2-naphthylamine when it is released from aminoacyl-2-naphthylamides under the hydrolytic action of these enzymes. Values of enzymatic activities and kinetic constants are si...

A comparative study of brain aminopeptidase activity between 18 month old male rats and young adults of 3 months has been carried out utilizing the arylamides Leu-, Arg-, Lys-, Tyr- and Asp-beta-naphthylamide as substrates. Statistical analysis of results showed no significant differences either in areas studied or for enzymatic activities detected...

Aminopeptidase activity was assayed in several rat brain regions and serum during the estrous cycle. Significant changes are present in the occipital cortex, hypothalamus, pituitary gland and serum. These results suggest that aminopeptidase activity plays a part in the hormonal changes that take place in this cycle.

The participation of noradrenaline (NE) and serotonine (5-HT) in self-stimulation (SS) of the medial prefrontal cortex (MPC) in the rat has been studied. Three groups of rats with bilateral electrodes implanted into the MPC were used in these experiments. In one of the groups, electrodes were also implanted into the locus coeruleus. In the first gr...