Magnesium Ions Exert a Central Role in Integrating Adenosine Receptor Occupancy with the Inhibition of Adenylate Cyclase

Purines ◽  
1985 ◽  
pp. 203-214 ◽  
Author(s):  
Siu-Mei Helena Yeung ◽  
Lynn T. Frame ◽  
J. Craig Venter ◽  
Dermot M. F. Cooper
Keyword(s):  
Adenylate Cyclase ◽  
Adenosine Receptor ◽  
Receptor Occupancy ◽  
Magnesium Ions

REGULATION OF RECEPTOR-OPERATED Ca2− CHANNEL OPENING IN HUMAN PLATELETS

1987 ◽  
Author(s):  
Katrina J Moffat ◽  
D Euan MacIntyre
Keyword(s):  
Adenylate Cyclase ◽  
Contrast Agents ◽  
Guanylate Cyclase ◽  
Receptor Occupancy ◽  
Human Platelets ◽  
Regulatory Mechanisms ◽  
Receptor Interaction ◽  
Thrombin Receptors ◽  
Channel Opening ◽  
Camp And Cgmp

Agonist-induced elevation of the platelet intracellular free Ca2+ concentration ([Ca2−]i), as monitored using quin2, is not electrically mediated and is attenuated by removal of extracellular Ca2− and by lanthanides (e.g Gd3−).Collectively these data suggest that elevation of [Ca2−]i in platelets derives in part via influx of external Ca2−presumably through a receptor-operated Ca2− channel (ROC). Hal lam & Rink (FEBS Lett. 186: 175: 1985) showed that Mn2−also enters platelets via these ROC. To investigate the possible regulatory mechanisms that govern ROC status, we utilized quin2-labelled human platelets suspended in a Ca2+-free Hepes buffered Tyrodes solution, and monitored agonist-induced Mn2+-mediated quenching of quin2 fluorescence as an index of ROC opening.Thrombin (Th, 0.01-1 U/ml), Vasopressin (VP, 10-1000 nM) and the TxA2-mitnetic, EP171 (1-100 nM) all induced ROC opening which occurred rapidly (<30s), was maximal within 30-60s and thereafter declined. Gd3+ (≤2 mM) markedly impaired this Mn2ࢤ-mediated quenching of quin2 fluorescence induced by all 3 agonists. The adenylate cyclase stimulant PGD2 (3-3000 nM) and the guanylate cyclase stimulant sodium nitroprusside (0.01-10 μM) impaired ROC opening induced by Th (0.5 U/ml), VP (100 nM) and EP171 (25 nM) whether added to platelets ≤120sbefore or 30s after the agonists. In contrast, agents that selectively antagonize, at the receptor level, the effects of VP (e.g. d(CH2)5Tyr Me AVP, 10 ¼H) or EP171 (e.g.EP092, 250nM), or that inhibit the action of Th(e.g. Hirudin 1 U/ml)only impaired ROC opening when added to platelets simultaneously with or before the agonist.These results indicate that, although initiated by agonist-receptor interaction, maintenance of the open state of ROC in human platelets does not require continued receptor occupancy or activation by agonist. Moreover, besides acting to impair the transduction processes initiated following occupancy by agonist of platelet Vi, TP and Thrombin receptors, cAMP-and cGMP-dependent reactions also can terminate or otherwise limit opening of ROC.

scholarly journals Stimulus-response uncoupling in the neutrophil. Adenosine A2-receptor occupancy inhibits the sustained, but not the early, events of stimulus transduction in human neutrophils by a mechanism independent of actin-filament formation

1992 ◽  
Vol 281 (3) ◽  
pp. 631-635 ◽  
Author(s):  
B N Cronstein ◽  
K A Haines
Keyword(s):  
Actin Filament ◽  
Adenosine Receptor ◽  
Actin Filaments ◽  
Cytochalasin B ◽  
Receptor Occupancy ◽  
Neutrophil Activation ◽  
Filament Formation ◽  
Stimulus Response ◽  
Adenosine A2 Receptor ◽  
A2 Receptors

Generation of superoxide anion (O2-) in response to occupancy of neutrophil chemoattractant receptors requires both early events (‘triggering’) and sustained signals (‘activation’). We have previously demonstrated that occupancy of adenosine A2 receptors inhibits O2- generation by neutrophils. In parallel, adenosine-receptor occupancy promotes association of bound N-formylmethionyl-leucyl-phenylalanine (fMLP) receptors with the cytoskeleton, a process associated with termination of neutrophil activation (stimulus-response uncoupling). We undertook this study to determine whether inhibition of neutrophil function by adenosine-receptor occupancy requires intact actin filaments and to examine the effect of adenosine-receptor occupancy on the stimulated generation of intracellular signals involved in neutrophil triggering and activation. Occupancy of adenosine A2 receptors by 5′-N-ethylcarboxamidoadenosine (NECA, 1 microM) significantly increased (130 +/- 1% of control, P less than 0.001, n = 3) association of [3H]fMLP with cytoskeletal preparations. Cytochalasin B (5 micrograms/ml), an agent which disrupts actin filaments, completely blocked association of [3H]fMLP with cytoskeletal preparations, as previously reported. However, NECA markedly increased association of [3H]fMLP with the cytoskeleton even in the presence of cytochalasin B (P less than 0.0002). Moreover, NECA did not significantly affect either the early (30s) or the late (5 min) formation of actin filaments after stimulation by chemoattractant (fMLP, 0.1-100 nM). Cytochalasin B markedly inhibited actin-filament formation by stimulated neutrophils, and NECA did not reverse the effect of cytochalasin B on actin-filament formation. Adenosine-receptor occupancy did not affect the rapid peak in diacylglycerol generation (less than or equal to 15 s) from either [3H]arachidonate- or [14C]glycerol-labelled phospholipid pools. However, as would be predicted if occupancy of the adenosine receptor was a signal for early termination of cell activation, NECA (1 microM) markedly diminished the slow sustained generation of diacylglycerol. These results suggest that adenosine-A2-receptor occupancy does not affect triggering of the neutrophil, but that occupancy of adenosine receptors is an early signal for the termination of neutrophil activation, i.e. the ‘premature’ finish of signal transduction. Moreover, these data indicate that at least two pathways are available for increasing the association of ligated chemoattractant receptors with the cytoskeleton of neutrophils: F-actin-dependent and -independent.

Na+ amplifies adenosine receptor-mediated inhibition of adipocyte adenylate cyclase

1981 ◽  
Vol 71 (1) ◽  
pp. 157-160 ◽  
Author(s):  
Klaus Aktories ◽  
Günter Schultz ◽  
Karl H. Jakobs
Keyword(s):  
Adenylate Cyclase ◽  
Adenosine Receptor

scholarly journals Ethanol alters the adenosine receptor-Ni -mediated adenylate cyclase inhibitory response in rat brain cortex in vitro

FEBS Letters ◽  
1987 ◽  
Vol 219 (2) ◽  
pp. 296-300 ◽  
Author(s):  
F. Bauché ◽  
A.M. Bourdeaux-Jaubert ◽  
Y. Giudicelli ◽  
R. Nordmann
Keyword(s):  
Adenylate Cyclase ◽  
Rat Brain ◽  
Adenosine Receptor ◽  
Brain Cortex ◽  
Inhibitory Response ◽  
Rat Brain Cortex
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