Enzyme immunoassays for the estimation of adenosine 3′,5′ cyclic monophosphate and guanosine 3′,5′ cyclic monophosphate in biological fluids

Horton, Jeffrey K.; Martin, Ruth C.; Kalinka, S.; Cushing, A.; Kitcher, J. P.; O’Sullivan, Michael; Baxendale, P.M.

doi:10.1016/0022-1759(92)90268-x

Cited by 32 publications

(21 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cells were then lysed with 50 mM HCl for 30 min on ice. The competitive cAMP-enzyme-linked immunosorbent assay was performed according to a described procedure (33).…”

Section: Methodsmentioning

confidence: 99%

Cannabinoid Receptor Type 1- and 2-mediated Increase in Cyclic AMP Inhibits T Cell Receptor-triggered Signaling

Börner

Šmída

Höllt

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The aim of this study was to characterize inhibitory mechanisms on T cell receptor signaling mediated by the cannabinoid receptors CB1 and CB2. Both receptors are coupled to G i/o proteins, which are associated with inhibition of cyclic AMP formation. In human primary and Jurkat T lymphocytes, activation of CB1 by R(؉)-methanandamide, CB2 by JWH015, and both by ⌬9-tetrahydrocannabinol induced a short decrease in cyclic AMP lasting less than 1 h. However, this decrease was followed by a massive (up to 10-fold) and sustained (at least up to 48 h) increase in cyclic AMP. Mediated by the cyclic AMP-activated protein kinase A and C-terminal Src kinase, the cannabinoids induced a stable phosphorylation of the inhibitory Tyr-505 of the leukocyte-specific protein tyrosine kinase (Lck). By thus arresting Lck in its inhibited form, the cannabinoids prevented the dephosphorylation of Lck at Tyr-505 in response to T cell receptor activation, which is necessary for the subsequent initiation of T cell receptor signaling. In this way the cannabinoids inhibited the T cell receptor-triggered signaling, i.e. the activation of the -chain-associated protein kinase of 70 kDa, the linker for activation of T cells, MAPK, the induction of interleukin-2, and T cell proliferation. All of the effects of the cannabinoids were blocked by the CB1 and CB2 antagonists AM281 and AM630. These findings help to better understand the immunosuppressive effects of cannabinoids and explain the beneficial effects of these drugs in the treatment of T cell-mediated autoimmune disorders like multiple sclerosis.Cannabinoids are discussed as drugs for the treatment of neuroinflammatory diseases and T cell-mediated autoimmune disorders such as, for example, multiple sclerosis. Their potential usefulness for such disorders is emphasized by the fact that cannabinoids affect functions of both neuronal and immune effector cells. Cannabinoids produce a variety of immunomodulatory effects (reviewed in Refs. 1 and 2). Among these effects, the cannabinoid-mediated inhibition of interleukin (IL)-2 2 production of activated T lymphocytes (3, 4) may be beneficial in the above mentioned diseases but on the other hand may also cause immunosuppression. Many effects of endogenous cannabinoids like anandamide and exogenous cannabinoids like ⌬9-tetrahydrocannabinol (THC), the psychoactive compound of Cannabis sativa, are mediated by the G i/o protein-coupled cannabinoid receptors CB1 and CB2. While CB1 was found to be expressed predominantly in neuronal cells and only to a lesser extend in peripheral cells like immune effector cells, CB2 was considered to be the "peripheral" cannabinoid receptor, being expressed in cells of the immune system (5). However, recent reports suggest the expression of CB2 in neuronal cells, as well (6, 7). Moreover, although normally expressed in very low amounts only, recent work from our laboratory demonstrated a massive up-regulation of functional CB1 receptors in T lymphocytes in response to cannabinoids themselves, IL-4, and T cell activation...

show abstract

“…The cells were then lysed with 50 mM HCl for 30 min on ice. The competitive cAMP-enzyme-linked immunosorbent assay was performed according to a described procedure (33).…”

Section: Methodsmentioning

confidence: 99%

Cannabinoid Receptor Type 1- and 2-mediated Increase in Cyclic AMP Inhibits T Cell Receptor-triggered Signaling

Börner

Šmída

Höllt

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Cells were treated with vehicle (DMSO, 0.1%) or BPIPP or other substances as indicated in DPBS containing 1 mM IBMX for 10 min, and then cyclic nucleotide accumulation was stimulated with activators of guanylyl or adenylyl cyclase as indicated for 4 -10 min. Medium was aspirated and cGMP was extracted by rapid freezing of the plates at Ϫ80°C in the presence of 50 mM sodium acetate (pH 4.0; 0.3 ml per well) and measured by ELISA (19). cAMP was extracted with 0.1 M HCl (0.3 ml per well) and measured with a cAMP assay kit (acetylation protocol; Cayman Chemical).…”

Section: Methodsmentioning

confidence: 99%

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Kots¹,

Choi²,

Estrella-Jimenez

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Cells were lysed with 50 mM HCl for 30 min on ice. Acetylation of the samples and cAMP ELISA were performed according to a described procedure (Horton et al, 1992).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Promoter Regions Regulating Basal and Interleukin-4-Inducible Expression of the Human CB1 Receptor Gene in T Lymphocytes

Börner

Bedini²,

Höllt³

et al. 2007

Mol Pharmacol

View full text Add to dashboard Cite

The majority of effects of cannabinoids are mediated by the two receptors CB1 and CB2. In addition to neuronal cells, CB1 receptors are expressed in T lymphocytes, in which they are involved in cannabinoid-induced T helper cell biasing. Although basally expressed only weakly in T cells, CB1 receptors are up-regulated in these cells by stimuli such as cannabinoids themselves. This effect is mediated by interleukin-4. In this study, we investigated basal and interleukin-4-inducible expression of the CB1 gene in T lymphocytes. In a promoter analysis, two regions [nucleotides (nts) Ϫ3086 to Ϫ2490 and nts Ϫ1950 to Ϫ1653] were identified, which suppress basal transcription of the gene in Jurkat T cells, whereas the region between nts Ϫ648 and Ϫ559 enhanced basal

show abstract

Enzyme immunoassays for the estimation of adenosine 3′,5′ cyclic monophosphate and guanosine 3′,5′ cyclic monophosphate in biological fluids

Cited by 32 publications

References 16 publications

Cannabinoid Receptor Type 1- and 2-mediated Increase in Cyclic AMP Inhibits T Cell Receptor-triggered Signaling

Cannabinoid Receptor Type 1- and 2-mediated Increase in Cyclic AMP Inhibits T Cell Receptor-triggered Signaling

Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea

Analysis of Promoter Regions Regulating Basal and Interleukin-4-Inducible Expression of the Human CB1 Receptor Gene in T Lymphocytes

Contact Info

Product

Resources

About