Biomedical subjects

Alicia Rivera

Publications and source records attributed to Alicia Rivera.

21 records · Page 2Linked to original sources

PubMed2002

Dopamine D4 receptors are heterogeneously distributed in the striosomes/matrix compartments of the striatum.

Two important aspects of striatal function, exploratory behaviour and motor co-ordination, require the integrity of the dopamine D4 receptor subtype. These receptors are also implicated in the pathophysiology of certain neuropsychiatric disorders. However, the distribution of D4 receptors in the striatum has not yet been described and this situation impairs our understanding of the anatomical substrate in which D4 receptors function. We developed a D4 receptor-specific antibody that has permitted us to investigate the regional and cellular localization of the receptor in the neostriatum of the rat, mouse, cat and monkey. The subcellular distribution and the synaptic organization of this receptor were also determined in the rat striatum. We found moderate levels of D4 receptor expression in the caudoputamen and lower levels in the nucleus accumbens. These receptors were expressed in cell bodies and in the neuropil and were heterogeneously distributed among different striatal compartments, being more abundant in striosomes than in the matrix. At the subcellular level, the receptor immunoreactivity was mainly localized to dendritic shafts and spines. The prominent immunoreactivity observed in the striosomes indicates that integrative processes involved in D4-mediated limbic behaviours occurs through the striosomes rather than accumbens, whereas the motor behaviour is based in the striatal matrix.

Animals↗

PubMed2002

Molecular phenotype of rat striatal neurons expressing the dopamine D5 receptor subtype.

Dopamine is one of the principal neurotransmitters in the basal ganglia, where it plays a critical role in motor control and cognitive function through its interactions with the specific dopamine receptors D1 to D5. Although the activities mediated by most dopamine receptor subtypes have already been determined, the role of the D5 receptor subtype in the basal ganglia has still not been established. Furthermore, it is often difficult to distinguish between dopamine D5 and D1 receptors as they are stimulated by the same ligands, and they have a similar molecular structure and pharmacology. In an effort to understand the differences between these two receptor subtypes, we have studied the distribution of neurons containing D5 receptors in the striatum, and their molecular phenotype. As a result, we show that the D5 receptor subtype is present in two different populations of striatal neurons, projection neurons and interneurons. Overall, the abundance of this receptor subtype in the striatum is low, particularly in striatal projection neurons of both the direct and indirect projection pathways. In contrast, the expression of D5 receptors in striatal interneurons (cholinergic, somatostatin- or parvalbumin-positive neurons) is high, while low to moderate expression was observed in calretinin-positive neurons. Our results demonstrate the presence of D5 receptors in all the striatal cell populations so far described, although at different intensities in each. The fact that a large number of striatal neurons express the D5 receptor subtype suggests that this receptor fulfils an important function in the process of integrating information in the striatum.

Animals↗

PubMed2002

Red blood cell Na+/H+ exchange activity is insulin resistant in hypertensive patients.

A number of ion transport defects have been described in human red blood cells (RBC) from patients with essential hypertension. Insulin resistance is also frequently present in hypertensive patients and insulin levels in vitro correlate with red blood cell Na+/H+ exchange (NHE) activity. We studied the kinetics of insulin-stimulated NHE activity in freshly isolated RBC from 14 patients with essential hypertension and 8 normotensive subjects. We measured an estimate of maximal activity (Vmax) for NHE activity as net Na+ influx driven by an outward H+ gradient in acid-loaded and Na+-depleted erythrocytes. NHE activity was significantly greater in hypertensives than in normotensives (22.0 vs 14.5 mmol/L cell x h, respectively; P<0.01). When RBC were pre-incubated with a physiologic dose of insulin (100 microU/mL), NHE activity increased significantly in both groups but the increase was greater in normotensives than in hypertensives (9.6 vs 8.5 mmol/L cell x h, respectively; P < 0.05). Phosphatidylinositol-3 kinase (PI-3 kinase) inhibitors, wortmannin and LY294,002, had no effect on basal NHE activity but similarly and significantly inhibited insulin-stimulated NHE activity in both normal and hypertensive subjects. Insulin increased the Km for extracellular Na+ in normotensive subjects but not in hypertensive patients. In addition, the dose response curve for insulin and NHE activity showed that the curve for hypertensive patients was shifted rightward in relation to the normotensive subjects. These data suggest that insulin stimulates RBC NHE activity in vitro and this activation is mediated via a pathway that includes activation of PI-3 kinase. Hypertensive patients have elevated basal NHE activity but a blunted response to insulin suggesting that RBC may be a model to study insulin resistance in essential hypertensive patients.

Adult↗