Lysophosphatidic acids. II. Interaction of the effects of adenosine diphosphate and lysophosphatidic acids in dog, rabbit, and human platelets.
In order to explore a possible relationship between platelet aggregation induced by lysophosphatidic acid (LPA) and that induced by adenosine diphosphate (ADP), we have studied the influence of palmitoyl-LPA (P-LPA) on platelets from dogs and rabbits and on human platelets made refractory to LPA. Dog platelets did not aggregate with P-LPA alone, but P-LPA enhanced ADP aggregation, and after a small dose of ADP, P-LPA was itself effective in causing aggregation and internal contraction in dog platelets. Rabbit platelets showed no response to P-LPA alone, but, as with dog platelets, P-LPA enhanced ADP aggregation. In addition, when P-LPA was added during or immediately after ADP aggregation, it caused a contraction within the platelets and a small wave of aggregation by itself. P-LPA added to human platelets caused aggregation without the need for ADP. However, when a small dose of P-LPA was added to human platelets and the wave of aggregation was allowed to reverse, these platelets subsequently were unresponsive to P-LPA, although they showed an enhanced response to ADP. The addition of a small dose of ADP to the P-LPA refractory platelets partially reversed the refractory state, and the platelets then showed aggregation with P-LPA. The results demonstrate that ADP and P-LPA have significant interactions in their effects on platelets. These interactions are discussed in terms of a two-component mechanism for the ADP-induced intracellular calcium flux, LPA, or possibly phosphatidic acid, being one component.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D006801:Humans; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013045:Species Specificity
D003839:Deoxyadenosines; D010712:Phosphatidic Acids; D000244:Adenosine Diphosphate; D002118:Calcium