Wortmannin inhibits platelet aggregation produced by interaction of gamma-aminobutyric acid and the calcium tonophore, A23187.
Platelet aggregation by gamma-aminobutyric acid (GABA) agonists combined with a calcium ionophore was studied. GABA, baclofen and mucimol markedly amplified aggregatory responses to a subthreshold concentration of the ionophore, A23187. This effect was inhibited by wortmannin, a blocker of phosphoinositide 3-kinase. However, several antagonists of GABA receptors had no effect on the response, and benzodiazepines inhibited aggregation. These results suggest that the GABA effect is not mediated by traditional neuronal GABA receptors. We propose that wortmannin inhibits aggregation at a nexus downstream from membrane mechanisms triggered by the GABA-A23187 interaction.
Saeed
S A
SA
Department of Physiology and Pharmacology, The Aga Khan University, Karachi, Pakistan. arshd.saeed@aku.edu
Connor
J D
JD
Rasheed
H
H
Gilani
A H
AH
Lodhi
S
S
Ali
S S
SS
Rashid
S
S
Khan
E
E
Shah
B H
BH
D000730:Androstadienes / Q000494:pharmacology*; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000730:Androstadienes; D000001:Calcimycin; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000077191:Wortmannin; D005680:gamma-Aminobutyric Acid