Cyclic AMP metabolism in cholesterol-rich platelets.

Sinha, Asru K.; Shattil, Sanford J.; Colman, Robert W.

doi:10.1016/s0021-9258(17)40389-9

Cited by 122 publications

(9 citation statements)

References 26 publications

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“…In biological and reconstituted membranes, the flexible hydrocarbon chains of phospholipids stabilize the structure of integral protein in the membrane while the rigid molecule of cholesterol is probably excluded from close proximity to the membrane protein. The effects of cholesterol on the enhancement of membrane protein activity are evident in transport systems (Saito & Silbert, 1979) and enzymatic systems (Sinha et al, 1977). In these unique cases, cholesterol seems to play a rather specific role in activation of membrane protein.…”

Section: Discussionmentioning

confidence: 99%

Interaction of differently oriented lipids in monolayer: mixed monolayers of 16-(9-anthroyloxy)palmitic acid with phosphatidylcholine and cholesterol

Nakagaki¹,

Tomita²,

Handa³

1985

Biochemistry

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16-(9-Anthroyloxy)palmitic acid (16-AP) is a bifunctional molecule with carboxyl and 9-anthroyloxy groups attached at both ends of the hydrocarbon chain. At the air-water interface, in a monolayer, the 16-AP molecule has horizontal and vertical orientations, depending on the surface pressure of the monolayer. The miscibilities of 16-AP with dimyristoylphosphatidylcholine (DMPC), cholesterol (CH), and fatty acids in mixed monolayers were evaluated in investigations of monolayer phase transitions. Lipid molecules with flexible hydrocarbon chains, i.e., DMPC and fatty acids, formed homogeneous mixed monolayers with horizontally oriented 16-AP. On the other hand, the rigid molecule, CH, could not accommodate the horizontally oriented 16-AP in a monolayer, and there was a phase separation from 16-AP. In biological and reconstituted membranes, preferential binding of phospholipid to the integral protein and exclusion of cholesterol in close vicinity of the membrane protein have been recognized. On the basis of this work, it can be expected that flexible lipids readily accommodate the rough hydrophobic surface of integral proteins and stabilize the structure of the protein, while rigid lipids such as cholesterol are removed from the immediate environment of the membrane protein, if the protein does not interact specifically with the rigid lipids.

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Section: Discussionmentioning

confidence: 99%

Interaction of differently oriented lipids in monolayer: mixed monolayers of 16-(9-anthroyloxy)palmitic acid with phosphatidylcholine and cholesterol

Nakagaki¹,

Tomita²,

Handa³

1985

Biochemistry

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“…We initially hypothesized that changes in cAMP generation might explain the change in platelet responsiveness because it had been reported that incorporation of cholesterol into platelet membranes increases basal adenylate cyclase activity while abolishing NaFand PGEi-stimulated activity (Sinha et al, 1977). In that previous report, cyclase activity was assayed in platelet sonicates with both Mg2+ and ATP at 2 mM.…”

Section: Discussionmentioning

confidence: 99%

“…Platelet mixtures (0.5 mL) were placed in a cylindrical cuvette 3 mm in diameter containing a silicone-coated stirring bar. Aggregation was recorded as the percent decrease in light transmittance as platelet aggregates formed in an aggregometer (Sinha et al, 1977).…”

Section: Methodsmentioning

confidence: 99%

“…Incubation of platelets in vitro with lipid dispersions containing 2.2 mol of cholesterol/mol of phospholipid (C/PL = 2.2) re-0006-2960/78/0417-5269S01.00/0 © 1978 American Chemical Society suits in a selective increase of platelet membrane cholesterol (Shattil et al, 1975). Platelets that have been enriched with cholesterol in this manner are altered in several ways: they become more responsive than normal to platelet aggregating agents [e.g., (-)-epinephrine and ADP] (Shattil etal., 1975); they have decreased membrane fluidity (Shattil & Cooper, 1976) , reflecting an increase in order within lipid-lipid interactions (Shinitzky & Barenholz, 1978); and they have been reported to have altered adenylate cyclase (ATP pyrophosphate-lyase [cyclizing] EC 4.6.1.1) activity (Sinha et al, 1977) . In contrast, incubation of platelets with cholesterol-free phospholipid dispersions (C/PL = 0) results in a decrease in platelet membrane cholesterol, and this is associated with an increase in membrane fluidity and a decrease in responsiveness of these platelets to epinephrine (Shattil et al, 1975;Shattil & Cooper, 1976).…”

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confidence: 99%

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Relationships between membrane cholesterol, α-adrenergic receptors, and platelet function

Insel¹,

Nirenberg²,

Turnbull³

et al. 1978

Biochemistry

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“…Phosphodiesterase activities were assayed at 30 °C in a 0.1-mL reaction volume containing 50 mM Tris-HCl, pH 7.5, 20 mM MgCl2, 1 mg/mL BSA, and appropriate levels of tritiated cAMP or cGMP (usually about 50000 cpm/assay). Column fractions were assayed for cAMP phosphodiesterase activity by using a BaS04 precipitation as described by Sinha et al (1977). The assay was stopped by the addition of 0.2 mL of 0.2 M ZnS04, 0.2 mL of 0.2 M Ba(OH)2 was then added, and the BaS04 precipitate was collected by centrifugation for 3 min at 12000g in an Eppendorf centrifuge.…”

Section: Samples Of the Purified Cyclic Nucleotide Phosphodiesterasementioning

confidence: 99%

Purification and characterization of a human platelet cyclic nucleotide phosphodiesterase

Grant¹,

Colman²

1984

Biochemistry

118

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A cyclic nucleotide phosphodiesterase was extensively purified from the 100000g supernatant fraction of human platelets. The purification was 2500-3000-fold with 30% recovery of activity. The enzyme was isolated by DEAE-cellulose chromatography followed by adsorption to blue dextran-Sepharose and elution with cAMP. The protein has a molecular weight of 140 000 as determined by gel filtration. On NaDodSO4-containing polyacrylamide gels the major band is at 61 000 daltons, suggesting that the enzyme may exist as a dimer in solution under nondenaturing conditions. The enzyme requires Mg2+ or Mn2+ for activity. The calcium binding protein calmodulin does not stimulate hydrolysis of cAMP by this enzyme. The purified enzyme hydrolyzes both cAMP and cGMP with normal Michaelis-Menten kinetics with Km values of 0.18 microM and 0.02 microM, respectively. The hydrolysis of cGMP, however, is only one-tenth as rapid as the hydrolysis of cAMP. Cyclic GMP does not stimulate cAMP hydrolysis but instead is a potent competitive inhibitor of cAMP hydrolysis. The enzyme is also competitively inhibited by the phosphodiesterase inhibitors papaverine, 3-isobutyl-l-methylxanthine, and dipyridamole. The enzyme did not cross-react with an antibody raised to a cAMP phosphodiesterase isolated from dog kidney, indicating that the enzymes are not immunologically related. The inhibition of cAMP hydrolysis by cGMP suggests a possible regulatory link between these two cyclic nucleotides. One of the roles of cGMP in platelets may be to potentiate increases in intracellular cAMP by inhibiting the hydrolysis of cAMP by this enzyme.

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Cyclic AMP metabolism in cholesterol-rich platelets.

Cited by 122 publications

References 26 publications

Interaction of differently oriented lipids in monolayer: mixed monolayers of 16-(9-anthroyloxy)palmitic acid with phosphatidylcholine and cholesterol

Interaction of differently oriented lipids in monolayer: mixed monolayers of 16-(9-anthroyloxy)palmitic acid with phosphatidylcholine and cholesterol

Relationships between membrane cholesterol, α-adrenergic receptors, and platelet function

Purification and characterization of a human platelet cyclic nucleotide phosphodiesterase

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