concanavalin-a and zinc-chloride

Glial cells in fiber tracts express various functional transmitter receptors, e.g., got glutamate. However, little is known about their biophysical and pharmacological profile. Using the in situ patch-clamp technique, kainate- and AMPA-induced conductance changes of glial precursor cells in the rat corpus callosum were investigated to study these aspects. Precursor cells were identified by their voltage-gated currents and were easily discernable from astrocytes and oligodendrocytes. Kainate induced two overlying effects in these cells: the activation of a cationic current and the block of potassium conductances. Cesium in the pipette solution blocked potassium conductances nearly completely and the ionic profile of the kainate-induced cationic current could be studied in detail. Full replacement of the sodium in the bath by calcium resulted only in a small kainate-induced (calcium) inward current flow, but the kainate-induced outward current carried by Cs+ was less affected reflecting a weak calcium permeability. The kainate response could be blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX) and millimolar zinc concentrations. Co-application of micromolar concentrations of zinc slightly enhanced the kainate-induced current, while Evans Blue was without any significant effect. Cyclothiazide increased the kainate response by a factor of x6 while concanavalin A did not enlarge it. The AMPA-induced current was amplified by a factor of x39 by cyclothiazide. The present data suggested the expression of weakly calcium-permeable AMPA receptors on glial precursor cells in the rat corpus callosum. Only a small fraction of the agonist-induced current could be seen without the appropriate blockers of receptor desensitization. An additional expression of kainate-preferring glutamate receptors could not be shown.

Topics: Animals; Benzothiadiazines; Calcium; Chlorides; Concanavalin A; Corpus Callosum; Diuretics; Evans Blue; Kainic Acid; Neuroglia; Patch-Clamp Techniques; Quinoxalines; Rats; Receptors, AMPA; Receptors, Kainic Acid; Sodium Chloride Symporter Inhibitors; Zinc Compounds

Since it is well known that both zinc ions and bacterial immunostimulants influence the function of the immune system, in the present study we investigated the immunomodulating activity of a new analog of peptidoglycan monomer (PGM), in which the basic molecule was linked to zinc (PGM-Zn). Its effects in BALB/c mice, aged 10-12 months, were compared with the effects of equimolar doses of PGM and ZnCl2. The treatment lasted 26 days (one i.p. injection every fifth day). The results showed that PGM-Zn may markedly enhance antibody production to sheep red blood cells, as well as spontaneous and concanavalin A (ConA)-induced blastogenesis. The generation of plaque-forming cells in individual mouse was positively correlated with the expression of class II antigens in the liver and negatively correlated with the total quantity of hepatic proteins. PGM-Zn also induced the appearance of peritoneal macrophages, which in cocultures with syngeneic splenocytes were less able to enhance the spontaneous, and particularly the ConA-induced blastic transformation. The enhancing activities of PGM-Zn were in some respects more closely correlated with the action of PGM, whereas the induction of suppressive macrophages resembled more the activity of ZnCl2. The data emphasize that PGM-Zn may both stimulate and inhibit immunoregulative pathways by mechanisms which are not identical to those of PGM or ZnCl2.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Carbohydrate Sequence; Cells, Cultured; Chlorides; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Hemolytic Plaque Technique; Liver; Lymphocyte Activation; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Peptidoglycan; Spleen; Zinc Compounds

To study the effect of zinc on the proliferative response to polyclonal T cell mitogens, spleen cells from C57BL/6 mice were cultured with or without ZnCl2 and stimulated with graded doses of concanavalin A or phytohemagglutinin. Addition of 10(-4) M ZnCl2 inhibited proliferation whereas 10(-5) to 10(-6) M ZnCl2 did not modify the response to suboptimal doses of mitogen but increased DNA synthesis in cultures stimulated with high doses of mitogen (10 or 20 micrograms/ml of concanavalin A and 10 or 25 microliters/ml of phytohemagglutinin) which are supraoptimal for C57BL/6 mice, and inhibited proliferation in cultures of spleen cells from animals of this strain, low responder to T cell mitogens. In contrast, supplementation with ZnCl2 did not enhance the response to mitogen of spleen cells from high responder BALB/c mice. The enhancing effects of ZnCl2 on the proliferative response of C57BL/6 cells were not observed following depletion of adherent cells or in cultures supplemented with 5 X 10(-5) M 2-mercaptoethanol, both conditions capable of abrogating the inhibitory effect of high mitogen doses on the response of C57BL/6 cells.

Topics: Animals; Cells, Cultured; Chlorides; Concanavalin A; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred Strains; Phytohemagglutinins; Spleen; T-Lymphocytes; Zinc; Zinc Compounds