Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine which (if any) subtypes of leukemic blasts express a functional receptor for vasoactive intestinal peptide (VIP). Blasts harvested from bone marrow of 38 newly diagnosed patients were classified as acute lymphocytic leukemia (CALLA + pre-B-cell leukemia, CALLA-, pre-B-cell leukemia, T-cell leukemia) or acute myeloid leukemia based on cytochemical and histochemical markers. Of the 32 patients with lymphocytic leukemia, 22 expressed the VIP receptor as evidenced by VIP-mediated activation of adenylate cyclase in cell homogenates. Binding of 125I-VIP to ALL cells correlated with the ability of VIP to activate adenylate cyclase. The VIP receptor was not identified in myeloid blasts from any of six patients. Further correlation of 125I-VIP binding and VIP-mediated stimulation of adenylate cyclase was demonstrated in transformed cell lines: a pre-B-cell line (Nalm 6) and a T-cell line (Molt 4b) exhibited high-affinity binding of 125I-VIP and VIP-mediated activation of adenylate cyclase, whereas neither the histiocytic line (U937) nor the myelocytic line (HL60) appeared to express the VIP receptor. These observations suggest a role for VIP in the proliferation or differentiation of human T and B lymphocytes.
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PMID:Vasoactive intestinal peptide receptor expression on human lymphoblasts. 132 1

We have previously shown that stimulation of the Ti/CD3 receptor complex on human T-cells potentiates adenylate cyclase activation by adenosine or forskolin. Anti-CD2 receptor antibodies shared with anti-CD3 antibodies the ability to potentiate dose dependently the adenosine- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) accumulation, whereas stimulation of the CD45 receptor had no effect on cyclase activity. Modulation of the CD3 complex with anti-CD3 antibodies was found to decrease the CD2 receptor effect on adenylate cyclase activity greatly. The possible involvement of CD3-stimulated phospholipase C (PLC) activation on the cAMP potentiation was examined using HPB-ALL cells that express a CD3 complex with a defect coupling to PLC. Stimulation of the CD3 complex on HPB-ALL cells had only slight effects on adenosine-stimulated cAMP formation, whereas the effect on forskolin-stimulated cAMP was virtually unchanged. The CD3 effect was further analyzed in Jurkat cell membranes. In contrast to the results obtained after stimulation of intact cells, it was found that OKT3 stimulation of membranes did not potentiate the forskolin response. Finally, we tested whether inhibition of endogenous adenylate cyclase agonist production affected the CD3 effect. Inhibition of adenosine production or adenosine breakdown with 8-p-sulphophenyl theophylline (8-PST) or adenosine deaminase (ADA), respectively, did not alter the CD3 effects. Indometacin, which inhibits prostaglandin production, also had no effect. Together, these data show that stimulation of the CD2 receptor potentiates adenylate cyclase responses by a mechanism that is dependent on CD3 expression. Furthermore, the CD3 effect on cAMP appears to be mediated by two different mechanisms, one which is, and one which is not dependent on PLC. Finally, this effect is not due to an endogenous production of adenylate cyclase agonists.
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PMID:CD3-dependent increase in cyclic AMP in human T-cells following stimulation of the CD2 receptor. 167 13

Forskolin (FK), a reversible activator of adenylate cyclase, markedly enhanced the expression of interleukin-2 receptor (IL-2-R) on a human natural killer (NK)-like cell line, YT. The FK-induced increase in IL-2-R on YT cells closely correlated with an increase in intracellular cyclic AMP (cAMP) level, and was mimicked by dibutyryl cyclic AMP (dbcAMP). FK induced both high and low affinity IL-2-R on the cells. Using a cDNA for the IL-2-R as a probe, the FK-induced IL-2-R expression was shown to be associated with an increase in IL-2-R mRNA. FK also enhanced the IL-2-R expression on a human T lymphotrophic virus I (HTLV-I) positive T-cell line (YTA-1H) and augmented the phorbol ester-induced expression of IL-2-R on HTLV-I negative T-cell lines (HSB-2 and HPB-ALL). These results suggest the possibility that the stimulation of adenylate cyclase may serve as a pathway leading to activation of the IL-2-R gene in certain types of lymphocytes.
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PMID:Activation of interleukin-2 receptor gene by forskolin and cyclic AMP analogues. 303 78

Cannabinoid receptor (CB) expression was characterized in immunological cell and tissue preparations. Northern analysis revealed approximately 6-kb transcripts for CB1 (brain-type) in mouse spleen and brain and in rat cerebellum. CB1 was not detected in mouse thymus or rat spleen RNA by Northern analysis. CB2 (peripheral) was detected as a approximately 4-kb transcript in mouse spleen and thymus and as approximately 2.4-kb transcripts in rat spleen. Quantitation of CB2 transcripts in mouse spleen and thymus revealed approximately 4 x 10(3) and approximately 4 x 10(2) molecules/100 ng RNA, respectively, with no quantifiable CB2 in mouse brain. Conversely, CB1 was expressed in mouse brain (approximately 2 x 10(5) molecules/100 ng RNA) with lower expression in mouse spleen (approximately 2 x 10(2) molecules/100 ng RNA) and was not quantifiable in mouse thymus. Competition binding in intact mouse splenocytes demonstrated that nonradiolabeled cannabinoids CP-55940, Win-55212-2, CP-56667, delta 9-THC, and cannabinol all competed for receptor binding with 3H-CP-55940, a high-affinity nondiscriminating CB1 and CB2 receptor ligand. Based on previous findings which demonstrated a marked inhibition of T-cell-dependent immune responses by cannabinoids, primary T cells and several T-cell lines were characterized. Radioligand binding analysis identified 100-300 cannabinoid receptor binding sites/cell with an approximate Kd of 200-700 pM in purified splenic T cells which also exhibited cannabinoid-induced inhibition of adenylate cyclase. Northern analysis of human T-cell lines revealed approximately 2.4-kb CB2 mRNA transcripts but no CB1 in HPB-ALL cells, a cell line which also exhibited inhibition of adenylate cyclase by delta 9-THC. Conversely, Jurkat E6-1 cells expressed an unusual mRNA banding pattern for CB2 expressing three distinct transcript sizes, none of which were 2.4 kb, the size for human CB2. Jurkat also did not express CB1 mRNA and did not exhibit inhibition of adenylate cyclase when treated with delta 9-THC. Collectively, these results provide further evidence that CB2 is the predominant cannabinoid receptor within the immune system and that this form of the receptor is expressed on T cells.
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PMID:Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. 907 Mar 50