Adenyl cyclase in human platelets: Activity and responsiveness

Zieve, Philip D.; Greenough, William B.

doi:10.1016/0006-291x(69)90368-4

Cited by 99 publications

(26 citation statements)

References 5 publications

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“…These results were simiilar to those of earlier studies that also described an inhibition of cyclase activity by bovine thrombin (31)(32)(33). i'Iore recent work by Brodie et al., using human thrombin, also demonstrated an inhibition of cyclase activity in intact platelets by as little as 0.1 U/cc, a level comparable to that used in the present investigation.…”

Section: Discussionsupporting

confidence: 90%

Thrombin-Induced Increase in Intracellular Cyclic 3′,5′-Adenosine Monophosphate in Human Platelets

Droller¹,

Wolfe

1972

J. Clin. Invest.

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A B S T R A C T The present data disagree with earlier suggestions that thrombin's effect on platelets is to cause a decrease in intracellular cyclic 3',5'-adenosine monophosphate. Washed humani platelets or plateletrich plasma were incubated at 37°C with human thrombin. After centrifugation, the supernates were assayed for nucleotides and calcium released. The platelet pellets, anid in some experiments the supernates as well, were assayed by radioiimmunoassay for intracellular cyclic AMP. In the washed platelet systenm, increasing doses of thrombin to 0.5 U/cc induced increasing release of nucleotides and calcium. This was accompanied by an average twofold increase in intracellular cyclic AMP levels. Prostaglandin E1, which inhibited 30-50% of release, induced a four-to fivefold increase in cyclic AMP levels that was additive to the cyclic AMP-stimulatory effect of thrombin. Theophylline. which inhibited only 20-40%4 of nucleotide release, was synergistic with thrombin in the intracellular accumulation of cyclic AMP. The timiie-course of cyclic AMP accumulation in response to thrombinl was slower thani thrombin-induced nucleotide release. Similar findings were made in the platelet-rich plasma system where thrombin stimulation of nucleotide release also resulted in a marked accumulation of intracellular cyclic AMP. Thrombin did not appear to stimiiulate the release of intracellular cyclic AMP.The mechanism underlying these observations was not apparent. The thrombin had no measurable inhibitory effect on platelet phosphodiesterase activity in either intact washed cells or the platelet homogenate supernates. Furthermore, thrombin inhibited, rather than stimulated, platelet adenyl cyclase activity in both

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Section: Discussionsupporting

confidence: 90%

Thrombin-Induced Increase in Intracellular Cyclic 3′,5′-Adenosine Monophosphate in Human Platelets

Droller¹,

Wolfe

1972

J. Clin. Invest.

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“…Adenyl cyclase activity was 1.09 and 1.04 mnumoles cAMP formed per milligram protein/10 min after incubation of platelet membranes with and without 1 U/ml thrombin for 20 min respectively. Thrombin at 100 U/ml did inhibit adenyl cyclase 50-75% as reported previously (5,9).…”

Section: Introductionsupporting

confidence: 87%

“…Previous studies from several laboratories have indicated that human platelets contain adenyl cyclase and cyclic nucleotide phosphodiesterase (cAMP phosphodiesterase)' (1)(2)(3)(4)(5)(6). Compounds which affect the activity of these enzymes and, as a result, the concentrations of adenosine 3',5'-monophosphate (cyclic AMP, cAMP) in platelets also have marked effects on platelet aggregation (2, 6-10) and on the platelet release reaction (11).…”

Section: Introductionmentioning

confidence: 99%

“…These observations have led to the hypothesis that agents which inhibit platelet aggregation increase the concentration of cAMP in platelets by stimulating adenyl cyclase or by inhibiting cAMP phosphodiesterase, and agents which stimulate aggregation and release, decrease platelet cAMP by the opposite mechanisms. One difficulty in explaining the action of thrombin by this hypothesis is that 0.1-1.0 U/ml of thrombin induces aggregation and release in intact platelets while 10-200 U/ml of bovine thrombin are required to demonstrate inhibition of adenyl cyclase activity in disrupted platelet preparations (5,9). …”

Section: Introductionmentioning

confidence: 99%

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The Effects of Thrombin on Adenyl Cyclase Activity and a Membrane Protein from Human Platelets

Brodie¹,

Baenziger²,

Chase³

et al. 1972

J. Clin. Invest.

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A B S T R A C T Washed human platelets were incubated with 0.1-1.0 U/ml human thrombin and the effects on adenyl cyclase activity and on a platelet membrane protein (designated thrombin-sensitive protein) were studied. Adenyl cyclase activity was decreased 70-90% when intact platelets were incubated with thrombin. The Ti for loss of adenyl cyclase activity was less than 15 sec at 1 U/ml thrombin. There was no decrease of adenyl cyclase activity when sonicated platelets or isolated membranes were incubated with these concentrations of thrombin. Loss of adenyl cyclase activity was relatively specific since the activities of other platelet membrane enzymes were unaffected by thrombin. Prior incubation of platelets with dibutyryl cyclic adenosine monophosphate (AMP), prostaglandin El, or theophylline protected adenyl cyclase from inhibition by thrombin.Incubation of intact but not disrupted platelets with thrombin resulted in the release of thrombin-sensitive protein from the platelet membrane. The rapid release of this protein (Ti < 15 sec) at low concentrations of thrombin suggested that removal of thrombin-sensitive protein from the platelet membrane is an integral part of the platelet release reaction. This hypothesis is supported by the parallel effects of thrombin on adenyl cyclase activity and thrombin-sensitive protein release in the presence of dibutyryl cyclic AMP, prostaglandin Ei, and theophylline at varying concentrations of thrombin.

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“…A comparison of the NaFinduced secretion with the secretion induced by ionophore A23187 is tempting, since this inducer has also been shown to have a full secretagogue effect at pH 5.3 (Mirer & Stewart, 1977). Fluoride activates adenylate cyclase in platelet homogenates (Zieve & Greenough, 1969), but an enhanced cyclic AMP concentration has been shown to inhibit rather than to activate platelet function (Haslam, 1975). However, fluoride is not believed to activate adenylate cyclase in intact cells (Vigdahl et al, 1969).…”

Section: Statistical Treatment Ofresults Inmentioning

confidence: 99%

Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets

Mürer¹,

Davenport²,

Siojo³

et al. 1981

Biochemical Journal

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Adenyl cyclase in human platelets: Activity and responsiveness

Cited by 99 publications

References 5 publications

Thrombin-Induced Increase in Intracellular Cyclic 3′,5′-Adenosine Monophosphate in Human Platelets

Thrombin-Induced Increase in Intracellular Cyclic 3′,5′-Adenosine Monophosphate in Human Platelets

The Effects of Thrombin on Adenyl Cyclase Activity and a Membrane Protein from Human Platelets

Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets

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