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Journal of Clinical Investigation

Journal of Clinical Investigation

IF: 13.3
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Cyclic 3',5'-adenosine monophosphate in human blood platelets. II. Effect of N6-2'-o-dibutyryl cyclic 3',5'-adenosine monophosphate on platelet function.

Published:1 January 1971 DOI: 10.1172/JCI106467 PMID: 4322665
E W Salzman, L Levine

Abstract

The relation of cyclic 3',5'-adenosine monophosphate to platelet function has been studied by investigating the influence of this compound and of its N(6)-2'-0-dibutyryl derivative on platelet aggregation and other aspects of platelet behavior after demonstration of adenyl cyclase activity in disrupted platelets. Dibutyryl cyclic AMP inhibited platelet aggregation induced by ADP, epinephrine, collagen, and thrombin. Cyclic AMP was also inhibitory but was less effective. The platelet "release reaction" was also inhibited; specifically, there was inhibition of the induction of platelet factor 3 activity and of the release of labeled 5-hydroxytryptamine. Platelet swelling produced by ADP was not inhibited. The action of dibutyryl cyclic AMP did not result from contamination with 5'-AMP, nor was it attributable to production of 5'-AMP by plasma enzymes. Dibutyryl cyclic AMP was degraded to 2'-O-monobutyryl cyclic AMP and to cyclic AMP in plasma, but plasma exhibited no cyclic nucleotide phosphodiesterase activity, and the production of 5'-AMP did not occur. The in vitro effects of dibutyryl cyclic AMP were associated with uptake of the compound by platelets. Adenyl cyclase activity of platelet homogenates was demonstrated with production of 9.27 x 10(-11) (+/-2.62 x 10(-11)) mole cyclic AMP per min per 10(10) platelets. The activity was increased by NaF and by prostaglandin PGE(1) and was decreased by epinephrine. The effect of epinephrine was blocked by phentolamine but not by propanolol. Adenyl cyclase activity was also inhibited by collagen, 5-hydroxytryptamine, and thrombin. ADP, dibutyryl cyclic AMP, and cyclic AMP did not alter adenyl cyclase activity. These observations are consistent with the hypothesis that platelet aggregation is favored by a decrease in platelet cyclic AMP and inhibited by an increase in cyclic AMP.

Substances (14)

Related products
Procduct Name CAS Molecular Formula Supplier Price
L(-)-Epinephrine 51-43-4 C9H13NO3 342 suppliers $16.60-$1386.00
Bucladesine sodium 16980-89-5 C18H25N5NaO8P 341 suppliers $12.00-$4560.00
ADP 58-64-0 C10H15N5O10P2 290 suppliers $11.00-$3120.00
Collagen 9007-34-5 NULL 257 suppliers $40.80-$1780.00
Adenosine 5'-monophosphate monohydrate 18422-05-4 C10H16N5O8P 198 suppliers $5.00-$1504.50
Thrombin 9002-04-4 NULL 196 suppliers $73.90-$58500.00
5-Hydroxytryptamine 50-67-9 C10H12N2O 172 suppliers $121.00-$2008.78
Phentolamine 50-60-2 C17H19N3O 98 suppliers Inquiry
Propanolol 525-66-6 C16H21NO2 70 suppliers Inquiry
O2''-Monobutyryl Cyclic AMP 15392-98-0 C14H18N5O7P 5 suppliers Inquiry

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