PMID- 10321720
OWN - NLM
STAT- MEDLINE
DCOM- 19990526
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 64
IP  - 16
DP  - 1999
TI  - Alpha2-adrenergic agonist modulation of [35S]GTPgammaS binding to 
      guanine-nucleotide-binding-proteins in human platelet membranes.
PG  - 1403-13
AB  - Alpha2-adrenoceptor (alpha2-AR)-regulated binding of the labelled GTP analog, 
      guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS), to 
      guanine-nucleotide-binding proteins (G proteins) was studied in human platelet 
      membranes. Under optimal conditions, the potent alpha2-AR agonist, 
      5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), increased the binding 
      of [35S]GTPgammaS up to approximately 1.8 fold, with half-maximal increase at 60 
      nM and was competitively inhibited by the alpha2-AR antagonist Rauwolscine. The 
      actions of both UK 14304 and Rauwolscine were modulated by monovalent and 
      divalent cation levels, as well as by the concentrations of GDP. [35S]GTPgammaS 
      binding induced by UK 14304 had a Kd value of 4.5 +/- 0.3 nM and a Bmax value of 
      4.15 +/- 0.40 pmol/mg protein. The rank order of potencies of adrenergic ligands 
      tested in stimulating [3S]GTPgammaS binding and inhibiting forskolin-stimulated 
      c-AMP accumulation was UK 14304> Guanabenz acetate> Oxymetazoline hydrochloride> 
      B-HT 920 dihydrochloride> p-Aminoclonidine hydrochloride> Clonidine 
      hydrochloride. The data presented indicate that enhancement of [35S]GTPgammaS 
      binding by alpha2-AR in human platelet membranes provides a simple functional 
      measure for receptor activation and can be used for determination of potencies 
      and efficacies of ligands at the alpha2-AR.
FAU - Gessi, S
AU  - Gessi S
AD  - Department of Clinical and Experimental Medicine, University of Ferrara, Italy.
FAU - Campi, F
AU  - Campi F
FAU - Varani, K
AU  - Varani K
FAU - Borea, P A
AU  - Borea PA
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfur Radioisotopes)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 451W47IQ8X (Sodium Chloride)
RN  - 4S9CL2DY2H (Brimonidine Tartrate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Adrenergic alpha-Agonists/*pharmacology
MH  - Blood Platelets/*metabolism/ultrastructure
MH  - Brimonidine Tartrate
MH  - Cell Membrane/*metabolism
MH  - Cyclic AMP/blood
MH  - GTP-Binding Proteins/*blood
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/*blood
MH  - Guanosine Diphosphate/pharmacology
MH  - Humans
MH  - Kinetics
MH  - Quinoxalines/pharmacology
MH  - Sodium Chloride/pharmacology
MH  - Sulfur Radioisotopes
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - S0024320599000740 [pii]
AID - 10.1016/s0024-3205(99)00074-0 [doi]
PST - ppublish
SO  - Life Sci. 1999;64(16):1403-13. doi: 10.1016/s0024-3205(99)00074-0.