Inhibition of adenylate cyclase activity during the reversible shape change in human platelets

Abstract

Washed platelets in the absence of physiological activators possess gravity inducible shape change, which is paralleled by an increase of phosphatidic acid (PA), polyphosphoinositides (PPI) and an inhibition of PGE1 and Gpp(NH)p- stimulated adenylate cyclase (AC) activity. Incubation of platelets at 37 degrees C for 1 hr decreases (32P)PPI and restores their response to low doses of thrombin (0.015 U/ml). Simultaneously an increase of PGE1- and Gpp(NH)p- stimulation of AC is observed. The relaxation of the platelets influences predominantly the cAMP levels without significantly affecting the dissociation constants of the stimulators. Forskolin-induced activation of AC is the same in stimulated and relaxed platelets. It is suggested that the initial increase of PA inhibits the coupling of regulatory and receptor proteins to AC and has no effect on the catalytic unit.