Inhibition of prostacyclin binding by cAMP and the regulation of the nucleotide binding by the prostonoid on platelet membranes

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6173235

Kahn, N N; Sinha, A K

Using (/sup 3/H) prostaglandin E/sub 1/ (PGE/sub 1/) as a probe for the interaction of prostacyclin (PGI/sub 2/) with its receptor on human blood platelet membrane, the authors found that the interaction was specific, saturable, reversible and attained equilibrium within 10 min at 23/sup 0/C. The binding of the autacoid to the membrane preparation was directly related to the degree of activation of adenylate cyclase. Addition of cAMP to the binding mixture removed almost 50% of the bound autacoid from the membrane within 5 min at 23/sup 0/C. The cAMP specific removal of the bound radiolabeled autacoid remained unaffected by the addition of cAMP-dependent protein kinase inhibitor (200 ..mu..g) indicating that the effect of the nucleotide was not mediated through the protein kinase. It was further found that not only cAMP removed bound (/sup 3/H)PGE, from the membrane but also the autacoid (100 nM) displaced 50% of the membrane bound (/sup 3/H)cAMP in 15 min at 23/sup 0/C. It was concluded that the activation of adenylate cyclase by PGI/sub 2/ in platelets leads to the inhibition of the enzyme by cAMP through decreased PGI/sub 2/ binding and conversely, the removal of the nucleotide by the autacoid results in the reactivation of the enzyme through increased prostonoid binding.

• Research Organization: Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
• OSTI ID: 6173235
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMP
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CELL CONSTITUENTS
CELL MEMBRANES
CYCLASES
ENZYME ACTIVITY
ENZYMES
FUNCTIONS
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYASES
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
NUCLEOTIDES
ORGANIC COMPOUNDS
PROSTAGLANDINS
PROTEINS
REACTION KINETICS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS