PMID- 14698049
OWN - NLM
STAT- MEDLINE
DCOM- 20040211
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 67
IP  - 2
DP  - 2004 Jan 15
TI  - Modulation of A1 adenosine receptor signaling by peroxynitrite.
PG  - 375-83
AB  - Nitric oxide (NO) is a gaseous free radical involved in many pathophysiological 
      processes. During oxidative stress, NO, its derivatives and adenosine are 
      released. Considering adenosine neuroprotective role in the central nervous 
      system (CNS) and toxicity of NO, we investigated the effect of a NO/peroxynitrite 
      (ONOO(-)) donor, 3-morpholinosydnonimine (SIN-1), on A(1) adenosine receptor 
      (A(1)AR) signaling pathway in rat cortical membranes. Membrane treatment with 
      0.5mM SIN-1 for various periods of time (0-240min) decreased specific binding of 
      the radiolabeled A(1)AR agonist, [3H]N(6)-cyclohexyladenosine ([3H]CHA), in a 
      time-dependent manner, reaching the steady state after 120min. The inhibitory 
      effect of SIN-1 was concentration-dependent, with an EC(50) value of 
      0.60+/-0.30mM (N=3). Membrane pre-incubation with the superoxide anion 
      (O(2)z.rad;(-)) scavenger superoxide dismutase (SOD) followed by SIN-1 addition, 
      abolished SIN-1 inhibition of [3H]CHA binding. Membrane treatment with 0.5mM 
      SIN-1 for 120min caused a significant 2-fold increase of the K(D) value for 
      [3H]CHA without changing the B(max) value. Moreover, pre-incubation of membranes 
      with A(1)AR agonists, CHA or N(6)-(2-phenylisopropyl)-adenosine (R-PIA) before 
      SIN-1 addition increased the inhibitory effect while the selective A(1)AR 
      antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) had no activity. Membrane 
      treatment with SIN-1 decreased receptor-stimulated guanosine 
      5'-O-(gamma[35S]thio)triphosphate ([35S]GTPgammaS) binding in a 
      concentration-dependent manner. This treatment influenced [35S]GTPgammaS binding 
      affinity for A(1)AR activated G(i) proteins in cortical membranes. These findings 
      suggest that ONOO(-) modulates A(1)AR signaling pathways by affecting receptor 
      G(i) protein coupling.
FAU - Giuntini, Janette
AU  - Giuntini J
AD  - Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, 
      Universita di Pisa, Pisa, Italy.
FAU - Giusti, Laura
AU  - Giusti L
FAU - Lucacchini, Antonio
AU  - Lucacchini A
FAU - Mazzoni, Maria R
AU  - Mazzoni MR
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Receptor, Adenosine A1)
RN  - 0 (Sulfur Radioisotopes)
RN  - 10028-17-8 (Tritium)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 5O5U71P6VQ (linsidomine)
RN  - D46583G77X (Molsidomine)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
SB  - IM
MH  - Animals
MH  - Central Nervous System/drug effects/metabolism
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/metabolism
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Male
MH  - Molsidomine/*analogs & derivatives/pharmacology
MH  - Nitric Oxide/pharmacology
MH  - Nitric Oxide Donors/pharmacology
MH  - Peroxynitrous Acid/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Adenosine A1/*metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Sulfur Radioisotopes
MH  - Tritium
EDAT- 2003/12/31 05:00
MHDA- 2004/02/12 05:00
CRDT- 2003/12/31 05:00
PHST- 2003/12/31 05:00 [pubmed]
PHST- 2004/02/12 05:00 [medline]
PHST- 2003/12/31 05:00 [entrez]
AID - S0006295203007433 [pii]
AID - 10.1016/j.bcp.2003.08.045 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2004 Jan 15;67(2):375-83. doi: 10.1016/j.bcp.2003.08.045.