Lanthanum stimulates the accumulation of cyclic AMP and inhibits secretion and thromboxane B2 formation in human platelets.
La3+ was found to inhibit the secretion of 5-hydroxytryptamine and the production of thromboxane B2 by washed platelets exposed to collagen or thrombin. In addition, La3+ inhibited secretion in response to sodium arachidonate, although the conversion of arachidonate to thromboxane B2 was not affected. La3+ was also found to enhance the accumulation of cyclic AMP under basal conditions and in response to prostaglandin E1, in washed platelets. The inhibition of cyclic AMP accumulation by ADP was prevented by La3+, suggesting that the effect of ADP on cyclic AMP metabolism was dependent upon the presence or flux of calcium at the platelet membrane. La3+ inhibited the activity of adenylate cyclase in platelet lysates both in response to prostaglandin E1 and to F-, indicating a possible effect at the catalytic subunit of the enzyme. None of the observed effects of La3+ could be reversed by the addition of Ca2+ up to 10 mM. The stimulation of cyclic AMP production by La3+ may largely explain the inhibitory effect of La3+ upon platelet secretion and thromboxane B2 production. These results also suggest that Ca2+ localised at the platelet plasma membrane may be important in the regulation of cyclic AMP metabolism.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000097:blood*; D005260:Female; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology*; D008297:Male; D012701:Serotonin / Q000097:blood* / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood*; D013931:Thromboxanes / Q000097:blood*
D013931:Thromboxanes; D012701:Serotonin; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D007811:Lanthanum; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium