Jan Dijk

Localization of Dopamine D2 Receptor in Rat Spinal Cord Identified with Immunocytochemistry and In Situ Hybridization

In the present study the distribution of dopamine D2 receptors in rat spinal cord was determined by means of immunocytochemistry using an anti‐peptide antibody, directed against the putative third intracellular loop of the D2 receptor and in situ hybridization (ISH) using a [35S]UTP labelled anti‐sense riboprobe. With the immunocytochemical technique, labelling was confined to neuronal cell bodies and their proximal dendrites. Strongest labelling was present in the parasympathetic area of the sacral cord and in two sexually dimorphic motor nuclei of the lumbosacral cord, the spinal nucleus of the bulbocavernosus and the dorsolateral nucleus. Moderately labelled cells were present in the intermediolateral cell column, the area around the central canal and lamina I of the dorsal horn. Weak labelling was present in the lateral spinal nucleus and laminae VII and VIII of the ventral horn. Except for the two sexually dimorphic motornuclei of the lumbosacral cord labelled motoneurons were not encountered. With the ISH technique radioactive labelling was present in many neurons, indicating that they contained D2 receptor mRNA. The distribution of these neurons was very similar to the distribution obtained with immunocytochemistry, but with ISH additional labelled cells were detected in laminae III and IV of the dorsal horn, which were never labelled with immunocytochemistry. The present study shows that the D2 receptor is expressed in specific areas of the rat spinal cord. This distribution provides anatomical support for the involvement of D2 receptors in modulating nociceptive transmission and autonomic control. Our data further indicate that D2 receptors are not directly involved in modulating motor functions with the exception, possibly, of some sexual motor functions.

MEASUREMENT OF THERMODYNAMIC NONIDEALITY ARISING FROM VOLUME-EXCLUSION INTERACTIONS BETWEEN PROTEINS AND POLYMERS

The effective thermodynamic radii of 23 ribosomal proteins from the 50 S subunit have been determined by gel chromatography on Sephadex G-50, thereby supporting the contention that most of the proteins of the 50 S ribosomal unit exhibit reasonably globular structures. To investigate further the usefulness of modelling proteins as spheres, the second virial coefficient describing excluded volume interactions of some ribosomal proteins with two inert polymers, polyethylene glycol (PEG) and dextran, has been determined by gel chromatography and/or sedimentation equilibrium techniques. Protein-polymer excluded volumes obtained with PEG 20000 and Dextran T70 as the space-filling solute are shown to conform reasonably well with a quantitative expression describing interaction between an impenetrable sphere and an ideal Brownian path (K.M. Jansons and C.G. Phillips, J. Colloid Interface Sci., 137 (1990) 75).

The solution structure of the guanine nucleotide exchange domain of human elongation factor 1β reveals a striking resemblance to that of EF-Ts from Escherichia coli

BACKGROUND In eukaryotic protein synthesis, the multi-subunit elongation factor 1 (EF-1) plays an important role in ensuring the fidelity and regulating the rate of translation. EF-1alpha, which transports the aminoacyl tRNA to the ribosome, is a member of the G-protein superfamily. EF-1beta regulates the activity of EF-1alpha by catalyzing the exchange of GDP for GTP and thereby regenerating the active form of EF-1alpha. The structure of the bacterial analog of EF-1alpha, EF-Tu has been solved in complex with its GDP exchange factor, EF-Ts. These structures indicate a mechanism for GDP-GTP exchange in prokaryotes. Although there is good sequence conservation between EF-1alpha and EF-Tu, there is essentially no sequence similarity between EF-1beta and EF-Ts. We wished to explore whether the prokaryotic exchange mechanism could shed any light on the mechanism of eukaryotic translation elongation. RESULTS Here, we report the structure of the guanine-nucleotide exchange factor (GEF) domain of human EF-1beta (hEF-1beta, residues 135-224); hEF-1beta[135-224], determined by nuclear magnetic resonance spectroscopy. Sequence conservation analysis of the GEF domains of EF-1 subunits beta and delta from widely divergent organisms indicates that the most highly conserved residues are in two loop regions. Intriguingly, hEF-1beta[135-224] shares structural homology with the GEF domain of EF-Ts despite their different primary sequences. CONCLUSIONS On the basis of both the structural homology between EF-Ts and hEF-1beta[135-224] and the sequence conservation analysis, we propose that the mechanism of guanine-nucleotide exchange in protein synthesis has been conserved in prokaryotes and eukaryotes. In particular, Tyr181 of hEF-1beta[135-224] appears to be analogous to Phe81 of Escherichia coli EF-Ts.

The Narrow Margins of the Dutch Drug Policy: A Cost-Benefit Analysis

In order to introduce more structure to the debate it seems worthwhile to make a rough cost-benefit analysis of the probable effects of the Dutch drug policy in various areas. A multi-disciplinary analysis of this nature makes it possible to bring together the arguments put forward by the protagonists from various perspectives and to some extent balance them against each other. In a traditional cost-benefit analysis the anticipated effects are assessed in financial terms. This is only possible to a very limited extent when it comes to drug policy. The article is limited to cataloguing as fully as possible the most significant pros and cons of the Dutch drug policy found in the literature on the subject. As a conclusion attention is paid to whether changes such as ‘decriminalisation’ or ‘re-criminalisation’ of drug use will yield a better cost-benefit analysis against the background of this overview.In order to introduce more structure to the debate it seems worthwhile to make a rough cost-benefit analysis of the probable effects of the Dutch drug policy in various areas. A multi-disciplinary analysis of this nature makes it possible to bring together the arguments put forward by the protagonists from various perspectives and to some extent balance them against each other. In a traditional cost-benefit analysis the anticipated effects are assessed in financial terms. This is only possible to a very limited extent when it comes to drug policy. The article is limited to cataloguing as fully as possible the most significant pros and cons of the Dutch drug policy found in the literature on the subject. As a conclusion attention is paid to whether changes such as ‘decriminalisation’ or ‘re-criminalisation’ of drug use will yield a better cost-benefit analysis against the background of this overview.

Criminal victimization in European cities

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The Development of Potent and Selective D-2 Agonists of the 2-Aminotetralin Group: Their Clinical Applications and their Use in the Isolation of the D-2 Receptor

In addition to the aporphine and ergot analogues the 2-aminotetralin derivatives have been one of the most important groups of compounds which have increased our understanding of the neurobiology of dopaminergic systems. The first report on the pharmacological activity of 2-aminotetralin (fig 1a) was published in 1889 by Bamberger and Filehe. More than 50 years later Bovet and Bovet-Nitti (1948) investigated the actions of various analogues of the parent compound.