PubMed Health⌕ Search

Biomedical subjects

J Sóvágó

Publications and source records attributed to J Sóvágó.

5 recordsLinked to original sources
PubMed2002

PET studies on the brain uptake and regional distribution of [11C]vinpocetine in human subjects.

OBJECTIVES: Vinpocetine is a compound widely used in the prevention and treatment of cerebrovascular diseases. It is still not clear whether the drug has a direct and specific effect on neurotransmission or its effects are due to extracerebral actions, such as changes in cerebral blood flow. The main objective of the present investigation was to determine the global uptake and regional distribution of radiolabelled vinpocetine in the human brain in order to explore whether it may have direct central nervous system effects. MATERIAL AND METHODS: Three healthy subjects were examined with positron emission tomography and [11C]vinpocetine. The regional uptake was determined in anatomically defined volumes-of-interest. The fractions of [11C]vinpocetine and labelled metabolites in plasma were determined using high pressure liquid chromatography. RESULTS: The uptake of [11C]vinpocetine in brain was rapid and 3.7% (mean; n = 4) of the total radioactivity injected was in brain 2 min after radioligand administration. The uptake was heterogeneously distributed among brain regions. When compared with the cerebellum, an a priori reference region, the highest regional uptake was in the thalamus, upper brain stem, striatum and cortex. Following an initial peak, the total concentration of radioactivity in blood was relatively stable with time, whereas the concentration of the unchanged compound decreased with time in an exponential manner. CONCLUSION: Vinpocetine, administered intravenously in humans, readily passes the blood-brain barrier and enters the brain. Its regional uptake and distribution in the brain is heterogeneous, indicating binding to specific sites. The brain regions showing increased uptake in the human brain correspond to those in which vinpocetine has been shown to induce elevated metabolism and blood flow. These observations support the hypothesis that vinpocetine has direct neuronal actions in the human brain.

Adult↗
PubMed2001

An overview on functional receptor autoradiography using [35S]GTPgammaS.

[35S]GTPgammaS binding autoradiography is a novel method to study the distribution and function of neurotransmitter receptors in tissue sections. This technique unifies the advantages of receptor-autoradiography and [35S]GTPgammaS binding, providing anatomical and functional information at the same time. Due to these two main features, it can also be called 'functional autoradiography'. [35S]GTPgammaS binding has long been used to study the first step of the intracellular signaling pathway, but until the mid 1990s it has only been performed on cell membrane extracts. Functional autoradiography evolved from this biochemical assay and ligand autoradiography, and is based on the increase in guanine nucleotide exchange at G-proteins upon agonist stimulation. With the technique, activation of G-protein-coupled receptors upon agonist binding can be detected, and, at the same time, the location of activated receptors can also be visualized. Thus only those presumably active G-protein-coupled receptors are visualized that can be involved in signal transduction. In the past 5 years the technique has become more and more frequently used in neuroscience, and it has been adapted to several receptors in different species, including also the human brain. [35S]GTPgammaS binding autoradiography can be used to describe the distribution of G-protein-coupled receptors. Some inferences on their coupling efficiency can also be drawn. Besides the localization of ligand binding sites, it provides information on the action of the ligand on the receptor: agonists, antagonists, and inverse agonists can clearly be distinguished. Moreover, [35S]GTPgammaS binding autoradiography can successfully be combined with other in vitro assays, like receptor autoradiography, in situ hybridization histochemistry, or even with biochemical and electrophysiological experiments. This review presents an overview on the history and the development of this technique. Its main advantages and limitations are summarized, together with a few basic technical questions. A number of experiments performed with [35S]GTPgammaS binding autoradiography so far, and some possible applications for the future, are also reviewed.

Animals↗