EFFECT OF CONCANAVALIN A ON 3H-5-HYDROXYTRYPTAMlNE UPTAKE IN RABBIT BLOOD PLATELETS : INTERACTION WITH ADENYLATE CYCLASE ACTIVITY

Abstract

Concanavalin A (Con A) was shown to have inhibitory effect on platelet adenylate cyclase as well as 5-hydroxytryptamine (5HT) uptake. These effects of Con A were antagonized by a-methyl-D-mannoside, a specific inhibitor of Con A binding to glycoprotein. The effect of Con A on adenylate cyclase was partial inhibition, and Con A had no effect on prostaglandin E1 stimulated activity, indicating the adenylate cyclase which is thought to be involved in 5HT uptake might be a minor component. The same result as Con A was demonstrated in the inhibitory effect of N-ethylmaleimide (NEM) on this activity. Impermeable sulfhydryl blocking reagents and iodoacetamide had no effect on 5HT uptake. It might be necessary for the sulfhydryl blocking reagent to pass through the cell membrane in order to exert its inhibitory effect on 5HT uptake. Furthermore, the inhibitory effect of Con A on 5HT uptake was antagonized by sulfhydryl reducing reagents and adenosine. It is postulated that a NEM sensitive, sub-membrane contractile protein system might mediate the effect of Con A, and Con A might inhibit platelet 5HT uptake by affecting the adenylate cyclase system through some possible transmembrane regulatory mechanism.