The Human Chemoattractant Complement C5a Receptor Inhibits Cyclic AMP Accumulation Through Gi and Gz Proteins

Shum, Jenny K.S.; Allen, Rodger A.; Wong, Yung Hou

doi:10.1006/bbrc.1995.1327

Cited by 31 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Even for the most efficient coupler of Ga16, the C5a receptor, U16-mediated stimulation of PLC (Amatruda et a!., 1993) required much higher concentrations of C5a than that for G,-mediated inhibition of adenyly! cyclase (Shum et al, 1995). In contrast, near equal efficacy for cAMP and TP accumulation was observed in similar cotransfection studies with Ga16 and the /I2-adrenergic or M2-muscarinic receptors (Offermanns and Simon, 1995).…”

Section: Discussionmentioning

confidence: 63%

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα₁₆‐Mediated Stimulation of Phospholipase C

Lee

Joshi

Chan

et al. 1998

Journal of Neurochemistry

105

View full text Add to dashboard Cite

The~i-opioidreceptor has recently been shown to stimulate phosphoinositide-specific phospholipase C via the pertussis toxin-sensitive G15 protein. Given the promiscuous nature of G16 and the high degree of resemblance of signaling properties of the three opioid receptors, both 6-and K-opioid receptors are likely to activate G16. Interactions of 6-and K-opioid receptors with G15 were examined by coexpressing the oploid receptors and Ga15 in COS-7 cells. The 6-selective agonist [D-Pen 2,DPen5] enkephalin potently stimulated the formation of mositol phosphates in cells coexpressing the 6-opioid receptorand Ga 16. The 6-opioid receptor-mediated stimulation of phospholipase C was absolutely dependent on the coexpression of Ga16 and exhibited appropriate ligand selectivity and dose dependency. Similar transfection studies revealed only weak stimulation by the pi-opioid receptor, whereas the K-opioid receptor produced moderate phospholipase C activity. Ga16 thus appeared to interact differentially with the three opioid receptors. Radioligand binding assays indicate that the 1i-opioid receptor was expressed at a lower level than those of the 6-and K-Opioid receptors. To examine if differential coupling to Ga16 is prevalent, a panel of G5-or G1-coupled receptors was coexpressed with Ga16 in COS-7 cells and assayed for agonist-induced stimulation of phospholipase C. Activation of a2-and /12-adrenergic, dopamine D1 and D2, adenosine A1, somatostatin-l and -2, C5a, formyl peptide, and luteinizing hormone receptors all resulted in stimulation of phospholipase C, with maximal stimulations ranging from 1 .5-to almost 17-fold. These findings suggest that the promiscuous Ga16 can in fact discriminate among different receptors and that such preferential interaction might in part be due to the abundance of receptors.

show abstract

Section: Discussionmentioning

confidence: 63%

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα₁₆‐Mediated Stimulation of Phospholipase C

Lee

Joshi

Chan

et al. 1998

Journal of Neurochemistry

105

View full text Add to dashboard Cite

show abstract

“…Coupling of the C5aR to G proteins was found to be pertussis toxin-resistant (42-44) as well as pertussis toxin-sensitive (43, 45-47) in PBMC (44 -46) or in transfected cells (42,43,47); in KC the mode of coupling has not been elucidated so far. The short-term C5a actions appear to be mediated by an increase in intracellular Ca 2ϩ (12,42,45,47), the long-term effects by an activation of the ras/raf/mitogen-activated protein kinase pathway (41) finally involving among other events the activation of NF-B (42).…”

Section: Mechanism Of the Synergistic Action Of C5a And Lps On Il-6 Rmentioning

confidence: 99%

“…CD14 is a GPI-anchored surface glycoprotein that cannot transmit a signal to the cell interior; signal transduction into the cell is achieved by the Toll-like receptor 4 initiating multiple intracellular signaling events, including the activation of NF-B. At LPS concentrations up to 5 ng/ml, the CD14 pathway is dependent on serum containing the LPS binding protein (47,48). However, in the present study, LPS at a concentration of 1 ng/ml was able to induce IL-6, TNF-␣, and IL-1␤ mRNA and stimulate the release of IL-6 and TNF-␣ protein in the absence of serum (Fig.…”

Section: Mechanism Of the Synergistic Action Of C5a And Lps On Il-6 Rmentioning

confidence: 99%

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

Mack¹,

Jungermann²,

Götze

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The effects of the anaphylatoxins C5a and C3a on the liver are only poorly characterized in contrast to their well known systemic actions. Recently, it has been demonstrated that the anaphylatoxin C5a enhanced glucose output from hepatocytes (HC) indirectly via prostanoid release from Kupffer cells (KC). In the present study, it is shown that recombinant rat C5a (rrC5a), together with LPS, activated the gene of the acute phase protein α2-macroglobulin (α2MG) in HC also indirectly via IL-6 release from KC. RrC5a alone increased neither IL-6 mRNA in nor IL-6 release from KC, whereas LPS alone did so. However, rrC5a synergistically enhanced the LPS-dependent increase in IL-6 mRNA and IL-6 release. Only rIL-6, but not TNF-α or IL-1β, enhanced α2MG mRNA in HC. In line with the actions of rrC5a and LPS on KC, conditioned medium of KC stimulated only with rrC5a did not increase α2MG mRNA in HC. However, medium of KC stimulated with rrC5a plus LPS induced α2MG mRNA expression in HC more strongly than medium from cells stimulated only with LPS; thus, C5a acted synergistically with LPS. The stimulatory effects of KC-conditioned medium could partially be inhibited by a neutralizing anti-IL-6 Ab, indicating that KC-derived IL-6 was a major mediator in C5a- plus LPS-elicited α2MG gene expression. These results suggest that C5a, besides enhancing glucose output via prostanoids, is involved in the initiation of the acute phase response in HC via proinflammatory cytokines from KC. This provides evidence for another important function of C5a in the regulation of hepatocellular defense reactions.

show abstract

“…The first two receptors couple to regulatory G proteins (8,9), whereas the C5L2 receptor has been shown to couple poorly to G protein-mediated signaling pathways (6,10). The distribution of these receptors is not restricted to leukocytes; they are also expressed on many types of nonmyeloid cells, including hepatocytes, lung epithelial cells, endothelial cells, brain astrocytes, and microglial cells, where they may mediate the involvement of the anaphylatoxins in several vascular, pulmonary, regenerative, and degenerative neurological conditions (11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

A Functional C5a Anaphylatoxin Receptor in a Teleost Species

Holland

Lambris

2004

The Journal of Immunology

View full text Add to dashboard Cite

The anaphylatoxins are potent, complement-derived low m.w. proteins that bind to specific seven-transmembrane receptors to elicit and amplify a variety of inflammatory reactions. C5a is the most potent of these phlogistic peptides and is a strong chemoattractant for neutrophils and macrophages/monocytes. Although lower vertebrates possess complement systems that are believed to function similarly to those of mammals, anaphylatoxin receptors have not previously been characterized in any nonmammalian vertebrate. To study the functions of C5a in teleost fish, we generated recombinant C5a of the rainbow trout, Oncorhynchus mykiss (tC5a), and used fluoresceinated tC5a (tC5aF) and flow cytometry to identify the C5a receptor (C5aR) on trout leukocytes. Granulocytes/Macrophages present in cell suspensions of the head kidney (HKL), the main hemopoietic organ in teleosts, showed a univariate type of receptor expression, whereas those from the peripheral blood demonstrated either a low or high level of expression. The binding of tC5aF was inhibited by excess amounts of unlabeled tC5a or tC5adesArg, demonstrating that sites other than the C-terminal of tC5a interact with the C5aR. Both tC5a and tC5adesArg were able to induce chemotactic responses in granulocytes in a concentration-dependent manner, but the desArg derivative was at least 10-fold less active. Homologous desensitization occurred after HKL were exposed to continuous or high concentrations of tC5a, with a loss of tC5aF binding and an 80% reduction in chemotactic responses toward tC5a. Pertussis toxin reduced the migration of HKL toward tC5a by 40%, suggesting only a partial involvement of pertussis toxin-sensitive Gi proteins in tC5a-mediated chemotaxis.

show abstract

The Human Chemoattractant Complement C5a Receptor Inhibits Cyclic AMP Accumulation Through Gi and Gz Proteins

Cited by 31 publications

References 0 publications

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα₁₆‐Mediated Stimulation of Phospholipase C

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα₁₆‐Mediated Stimulation of Phospholipase C

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

A Functional C5a Anaphylatoxin Receptor in a Teleost Species

Contact Info

Product

Resources

About

The Human Chemoattractant Complement C5a Receptor Inhibits Cyclic AMP Accumulation Through Gi and Gz Proteins

Cited by 31 publications

References 0 publications

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα16‐Mediated Stimulation of Phospholipase C

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα16‐Mediated Stimulation of Phospholipase C

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

A Functional C5a Anaphylatoxin Receptor in a Teleost Species

Contact Info

Product

Resources

About

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα₁₆‐Mediated Stimulation of Phospholipase C

Differential Coupling of μ‐, δ‐, and κ‐Opioid Receptors to Gα₁₆‐Mediated Stimulation of Phospholipase C