Details

Autor(en) / Beteiligte

• Huzoor-Akbar
• Navran, Stephen S.
• Chang, Jane
• Miller, Duane D.
• Feller, Dennis R.

Titel

Investigation of the effects of phospholipase C on human platelets: evidence that aggregation induced by phospholipase C is independent of prostaglandin generation, released ADP and is modulated by cyclic AMP

Ist Teil von

• Thrombosis research, 1982-08, Vol.27 (4), p.405-417

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

1982

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Effects and the mechanism of action of phospholipase C (PLC), from Clostridium perfringens , on washed human platelets were examined to better understand the role of PLC in platelet function. PLC caused aggregation and secretion of [ 14C]-5HT, without concomitant loss of cytoplasmic LDH, in a concentration dependent manner. P-nitrophenyl-phosphorylcholine, a substrate for PLC, blocked these responses in a concentration dependent manner. In other experiments hirudin, α-1-antitrypsin and soybean trypsin inhibitor did not inhibit PLC-induced activation of human platelets. PLC-induced aggregation and [ 14C]-5HT secretion was not inhibited by aspirin, a known inhibitor of prostaglandin biosynthesis. PLC-induced aggregation was selectively inhibited by analogs of 7,8-dihydroxybenzazepine and 7,8-methylenedioxybenzazepine in a concentration dependent manner. These two agents had no effect on arachidonic acid-induced aggregation. PLC-induced aggregation was not inhibited by apyrase, an enzyme which hydrolyzes ADP. In other experiments, PLC-treated platelets did not exhibit any platelet activating factor-like activity. Prostaglandin E 1 and trifluoperazine showed concentration dependent inhibitory effects on PLC-mediated aggregation and secretion of [ 14C]-5HT. These findings indicate that: a) PLC is capable of inducing aggregation and specific secretion of [ 14C]-5HT without causing lysis of platelets; b) mechanism of PLC-induced activation of platelets is independent of prostaglandin generation or action, released ADP, and PAF; and c) cyclic AMP plays a modulatory role in PLC-mediated secretion and aggregation of human platelets.