Hypothesis for the receptors of human blood platelet aggregation and its inhibition by structure-activity relationship.
We tried to clarify the size and the common charge distribution of the inhibition or stimulation of human platelet aggregation by structure-activity relationship. Numerous inhibiting and stimulating agents were able to enter the receptors. Inhibitory receptor had recess of 14 x 12.5 A in diameter. Stimulatory receptor had recess of 11 x 12 A in diameter. In the recess, there were three charges, two negative and one positive in the inhibitory receptor, and one negative and two positive in the stimulatory receptor, respectively. Charge distributions and conformation of inhibiting or stimulating agents were similar for the inhibitory agents, prostaglandin I2 (PGI2), PGD2, PGE1 adenosine and isoproterenol and conformation of the stimulating agents, thromboxane A2 (TXA2), platelet activating factor (PAF), adenosine diphosphate (ADP) and adrenaline. Each molecule had 3-10 inhibiting and stimulating conformations. The ratio of the number of conformations for inhibition and stimulating of platelet aggregation was highest for PGI2 which showed the strongest inhibitory activity. TXA2 was opposite in both respects.
Ojima
M
M
Department of Medicinal Research and Information, Ono Pharmaceutical Company Ltd., Osaka, Japan.
Tokuhiro
T
T
D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D008968:Molecular Conformation; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000737:chemistry / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin