Mordechai Sokolovsky

Endothelin in Cerebrospinal Fluid and Plasma of Patients in the Early Stage of Ischemic Stroke

BACKGROUND AND PURPOSEnEndothelin 1 (ET-1), a highly potent endogenous vasoactive peptide, exerts a sustained vasoconstrictive effect on cerebral vessels. Elevation of ET-1 in plasma has been reported 1 to 3 days after ischemic stroke. Since we assumed that a much faster and more intense response may be observed in the cerebrospinal fluid (CSF) and since an increase in concentration of ET-1 in the CSF may cause constriction of cerebral vessels and eventually influence the neurological outcome, we measured ET-1 values in the CSF within 18 hours of stroke onset and compared the values with those in the plasma.nnnMETHODSnTwenty-six consecutive patients with acute stroke were clinically evaluated according to the modified Matthew Scale and underwent two repeat CT scans. Within 5 to 18 hours of stroke onset, lumbar puncture and blood samples were concomitantly obtained and tested; ET-1 levels in CSF and plasma of these patients were analyzed by radioimmunoassay and compared with the levels of a control group of patients with no neurological disease.nnnRESULTSnThe mean CSF concentration of ET-1 in the CSF of stroke patients was 16.06 +/- 4.9 pg/mL, compared with 5.51 +/- 1.47 pg/mL in the control group (P < .001). It was significantly higher in cortical infarcts (mean, 17.7 +/- 4.1 pg/mL) than in subcortical lesions (mean, 10.77 +/- 4.1 pg/mL) (P < .001) and significantly correlated with the volume of the lesion (P = .003). The correlation between ET-1 levels in the CSF and the Matthew Scale score was less significant (P = .05). Plasma ET-1 level was not elevated in any group.nnnCONCLUSIONSnET-1 is found to be significantly elevated in the CSF of stroke patients during the 18 hours after stroke. No elevation was demonstrated in plasma at this time period. ET-1 may be used as an additional indicator of ischemic vascular events in the early diagnosis of stroke. The dissimilarity between the CSF and plasma ET-1 concentrations may lead also to an hypothesis that there is a vasoconstrictive effect on the cerebral vessels or a neuronal effect caused by ET-1 in the mechanism of the progression of brain ischemia.

1-Aminocyclopropane-1-carboxylic acid (ACC) mimics the effects of glycine on the NMDA receptor ion channel.

Les recepteurs du N-methyl D-aspartate jouent un role dans la plasticite neuronale et leur fonctionnement anormal est implique dans lepilepsie et les lesions ischemiques cerebrales. Le site effecteur de la glycine participe au complexe recepteur N-methyl D-aspartate. La glycine regule le canal cationique lie a ce recepteur. Les agonistes et les antagonistes de la glycine peuvent servir dagents therapeutiques lors du fonctionnement anormal des recepteurs N-methyl D-aspartate

Allosteric Interactions of Muscarinic Receptors and Their Regulation by Other Membrane Proteins

The complex nature of ligand binding to muscarinic acetylcholine (ACh) receptors in various tissues and the battery of compounds with antimuscarinic activity that affect muscarinic binding sites in a manner that does not fit simple competition (reviewed by Sokolovsky, 1984) suggest the possible existence of cooperative and allosteric interactions in the muscarinic system. In this review, we will discuss the current evidence and the experimental approaches (up to early 1987) employed to investigate such interactions in the muscarinic receptor system.

cGMP Formation in Rat Atrial Slices Is Ligand and Endothelin Receptor Subtype Specific

Involvement of a cGMP pathway in signal transduction stimulated by endothelins(ETs) and sarafotoxins (SRTXs) was examined in rat atrial slices. These peptides activated different receptor-binding sites (ET-1 and SRTX-b reacted with picomolar binding sites of the ET(A) receptor, and ET-3 and SRTX-c reacted with the nanomolar binding sites of the ET(B) receptor) to produce cGMP. ET-1 and SRTX-b stimulated an increase in cGMP levels via a Ca2+-dependent NO pathway involving a pertussis toxin-insensitive G protein, whereas ET-3 and SRTX-c elevated cGMP levels via a Ca2+-independent CO pathway involving a pertussis toxin-sensitive G protein. These results can best be explained in terms of formation of different ligand-receptor-G-protein complexes. The ligands had no effect on ventricular slices, indicating that these signal transduction mechanisms are unique to the atria.

Solubilization of endothelin/sarafotoxin receptors in an active binding form

We have recently characterized in rat heart and brain a high-affinity receptor for the cardiotoxic vasoconstrictor peptides, the endothelins (ET), and the sarafotoxins (SRTX). We examined several detergents for their ability to solubilize active receptors