Effect of lithium in vitro and after chronic treatment on human platelet adenylate cyclase activity: postreceptor modification of second messenger signal amplification.
LiCl in vitro markedly inhibits forskolin-stimulated human platelet adenylate cyclase activity by competing competitively with Mg2+ for a site on the catalytic subunit. The sensitivity of platelet membrane adenylate cyclase to lithium inhibition for individual manic patients was determined by the Dixon plot procedure: marked individual differences in sensitivity to lithium were observed pretreatment (0.66 mM-3.15 mM LiCl). After 3 weeks of continuous treatment with lithium in vivo a significant decrease in adenylate cyclase affinity for lithium was observed (pretreatment average Ki = 1.38 +/- 0.92 mM vs. treatment average Ki = 2.98 +/- 1.35 mM LiCl, n = 10). The clinical implications of these findings relating to chronic lithium exposure are discussed.
Ebstein
R P
RP
Moscovich
D
D
Zeevi
S
S
Amiri
Z
Z
Lerer
B
B
D000067956:Adenylyl Cyclase Inhibitors; D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects*; D002712:Chlorides / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D018021:Lithium Chloride; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D002712:Chlorides; D010716:Phosphatidylinositols; D011953:Receptors, Cyclic AMP; D008094:Lithium; D000242:Cyclic AMP; D018021:Lithium Chloride