Magnesium modifies the responses of platelets to inhibitory agents which act via cAMP.
This study has investigated the interaction of raised extracellular magnesium and agents which act via cAMP with respect to inhibition of platelet aggregation and effects on platelet cAMP accumulation. Iloprost (3 ng/ml) and PGD2 (0.2 microgram/ml) each caused time dependent increases in platelet cAMP which were significantly greater in the presence of 3 mM added MgSO4 (p < 0.01). Addition of ADP (5 microM) resulted in a fall in cAMP which remained higher in the presence of MgSO4 (p < 0.01). Forskolin (5 micrograms/ml) and DN9693 (100 microM) also caused increments in platelet cAMP but these responses were not influenced by added MgSO4. Addition of ADP resulted in a further increase in cAMP which was augmented by MgSO4 (p < 0.03). This increase was abolished by adenosine deaminase (1.2 U/ml). These experiments show that MgSO4 can modify the cAMP responses produced by iloprost and PGD2 and by forskolin and DN9693 when ADP is present. It appears that as well as inhibiting, ADP can also stimulate cAMP production under certain experimental conditions. This appears to be due to breakdown of ADP to adenosine.
Hardy
E
E
Department of Medicine, Queens Medical Centre, Nottingham, UK.
Glenn
J
J
Heptinstall
S
S
Rubin
P C
PC
Horn
E H
EH
D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction
D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; D005576:Colforsin; C049662:1,5-dihydro-7-(1-piperidinyl)-imidazo(2,1-b)quinazolin-2(3H)-one; D000242:Cyclic AMP; D008274:Magnesium; D016285:Iloprost; D015230:Prostaglandin D2