Direct evidence for the inhibition of platelet aggregation and release by intracellular cyclic AMP produced with a new photoactivatable derivative

D. Blache, J. Nargeot, J. M. Nerbonne

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

An increase in platelet cyclic AMP (cAMP) via stimulation of adenylate cyclase is thought to be the underlying mechanism by which potent prostaglandins i.e. PGD2, PGI2, inhibit platelet functions. We report here new and direct evidence for the inhibitory effects of cAMP on platelet aggregation and serotonin release. Washed platelets from rat were incubated with a new photoactivatable cAMP analogue (4,5-dimethoxy-2-nitrobenzyl ester); this compound is almost physiologically inert before irradiation and liberates free cAMP ('cAMP jumps') following light flashes. A single flash, delivered after 2 min incubation in 100-200 μM of the analogue, dramatically inhibited thrombin-induced aggregation, as compared with controls. Endogenous serotonin release, measured in the same samples by means of an electrochemically treated carbon electrode was undetectable after the cAMP jump. Pre-irradiated solutions added to platelets had no effect. The kinetics of the flash-induced effects were also studied. From these results we can conclude that: i) the photoactivatable cAMP derivative has to permeate through the platelet membrane; ii) the analogue remains photolabile; and, iii) intracellular cAMP, resulting from photolysis dramatically inhibits platelet aggregation and serotonin release. It is possible that cAMP exerts its effects by regulating cytoplasmic free calcium concentration and/or other actions affecting platelet activation.

Original languageEnglish
Pages (from-to)168-172
Number of pages5
JournalThrombosis and haemostasis
Volume55
Issue number2
StatePublished - Jan 1 1986
Externally publishedYes

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