270 DIPYRIDAMOLE AND PLATELET AGGREGATION
SIR,-Dr Moncada and Dr Korbut’ suggest that dipyridamole inhibits platelet aggregation by inhibiting phosphodiesterase, so potentiating the anti-aggregatory effect of prostacyclin which they believe to be mediated by cyclic A.M.P. We have evidence consistent with the idea that dipyridamole can inhibit thromboxane A2 synthesis.2 This may be an additional (or alternative) explanation for the potentiation of the effects of prostacyclin by this drug. In both smooth muscle and platelets thromboxane A2 may promote release of calcium into the cytoplasm from intracellular or membrane-bound stores.23 Prostacyclin seems to have a diametrically opposite effect, inhibiting release of intracellular calcium.4 Removal of thromboxane A2 by dipyridamole would therefore leave this effect of prostacyclin on calcium unopposed and would potentiate the inhibition of platelet aggregation by prostacyclin. D. F. HORROBIN A. I. ALLY M. S. MANKU
Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
SIR,-In this laboratory individual variations and drug effects related to human platelet susceptibility to prostacyclin (P.G.I2) have been investigated for some time. Preliminary results support the interesting findings reported by Dr Moncada and Dr Korbut. A log-log plot of p.G.I2 concentration in human platelet-rich plasma and the inhibition of the first wave of "threshold concentrations"’ A.D.p.-induced platelet aggregation yielded a linear relationship, and the concentration that inhibited the aggregation to 10% of peak aggregation (I,C’lO)
EFFECTS OF THEOPHYLLINE AND DIPYRIDAMOLE UPON
P.G.I2-INHIBITlON
OF PLATELET AGGREGATION
*p
SIR,-Dr Moncada and Dr Korbut’ suggest that dipyridamole inhibits platelet aggregation by inhibiting phosphodiesterase, so potentiating the anti-aggregatory effect of prostacyclin which they believe to be mediated by cyclic A.M.P. We have evidence consistent with the idea that dipyridamole can inhibit thromboxane A2 synthesis.2 This may be an additional (or alternative) explanation for the potentiation of the effects of prostacyclin by this drug. In both smooth muscle and platelets thromboxane A2 may promote release of calcium into the cytoplasm from intracellular or membrane-bound stores.23 Prostacyclin seems to have a diametrically opposite effect, inhibiting release of intracellular calcium.4 Removal of thromboxane A2 by dipyridamole would therefore leave this effect of prostacyclin on calcium unopposed and would potentiate the inhibition of platelet aggregation by prostacyclin. D. F. HORROBIN A. I. ALLY M. S. MANKU
Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
SIR,-In this laboratory individual variations and drug effects related to human platelet susceptibility to prostacyclin (P.G.I2) have been investigated for some time. Preliminary results support the interesting findings reported by Dr Moncada and Dr Korbut. A log-log plot of p.G.I2 concentration in human platelet-rich plasma and the inhibition of the first wave of "threshold concentrations"’ A.D.p.-induced platelet aggregation yielded a linear relationship, and the concentration that inhibited the aggregation to 10% of peak aggregation (I,C’lO)
EFFECTS OF THEOPHYLLINE AND DIPYRIDAMOLE UPON
P.G.I2-INHIBITlON
OF PLATELET AGGREGATION
*p
