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PubMedDate not supplied

Lymphocyte membrane adenosine receptors coupled to adenylate cyclase: properties and occurrence in various lymphocyte subclasses.

Lymphocytes possess membrane adenosine receptors through which this nucleoside or analogs activate adenylate cyclase. Several adenosine analogs - 5'-N-ethylcarboxamide adenosine (NECA), N6-(L-2-phenyl-isopropyl) adenosine (PIA), 2-chloro adenosine (Cl-Ado) - were tested on the adenylate cyclase of mouse thymocyte homogenates; the order of potencies: NECA greater than Cl-Ado greater than PIA is consistent with the order which has been assumed to be characteristic of Ra type adenosine receptors. The stimulation of thymocyte adenylate cyclase by NECA was biphasic while the responses to Cl-Ado and PIA were not, which suggests the existence of Ra sub-types of adenosine receptors. Moreover, these adenosine receptors were found to be present in several lymphocyte subclasses: mature and immature mouse thymocytes, B and T mouse splenocytes, human peripheral blood lymphocytes, and also in lymphoblastoid cell lines. No crucial differences were observed between the adenylate cyclase stimulations of the various population by NECA.

Adenosine↗

PubMedDate not supplied

Mechanisms of IL2 production impairment by lipoxygenase inhibitors in activated Jurkat cells.

We investigated the mechanisms by which lipoxygenase (LO) inhibitors decrease interleukin-2 (IL-2) production in Jurkat cells. We demonstrate that the inhibition, linked to blockade of the [Ca2+]i rise involving T cell receptor (TCR) triggering, resulted from the action of these compounds on the signal transduction pathway, upstream from inositol triphosphate synthesis. IL2 secretion induced by phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187, which bypasses the breakdown of inositol phospholipids induced by the ligand-receptor interaction, was still suppressed by LO inhibitors which implies that these drugs also have an inhibitory effect on other target(s). None of the three protein kinase C (PKC)-dependent events investigated was affected in Jurkat cells stimulated in the presence of LO inhibitors. Furthermore, these compounds did not inhibit IL2 production in PMA-treated Jurkat cells cultured with vanadate, which mimics the tyrosine kinase activation pathway and induces IL2 secretion. This suggests that in addition to their effect on the phosphatidylinositol diphosphate pathway-dependent [Ca2+]i rise, LO inhibitors might affect the tyrosine kinase pathway in TCR-activated Jurkat cells, but probably not the PKC-dependent pathway. These results are consistent with a role for LO metabolite(s) in signal transduction pathways.

Antigens, Differentiation, T-Lymphocyte↗