Phorbol 12,13-dibutyrate and 1-oleyl-2-acetyldiacylglycerol stimulate inositol trisphosphate dephosphorylation in human platelets

• Published in: The Journal of biological chemistry 1986-08, Vol.261 (23), p.10493-10495
• Main Authors: Molina y Vedia, L M, Lapetina, E G
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Cell physiology; Diglycerides - pharmacology; Fundamental and applied biological sciences. Psychology; Glycerides - pharmacology; Humans; Inositol 1,4,5-Trisphosphate; Inositol Phosphates - blood; Kinetics; Molecular and cellular biology; Phorbol 12,13-Dibutyrate; Phorbol Esters - pharmacology; Phosphorylation; Responses to growth factors, tumor promotors, other factors; Sugar Phosphates - blood; Tritium
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)67411-3

Inositol trisphosphate (IP3) is formed in response to specific agonists that cause activation of phospholipase C and degradation of phosphatidylinositol bisphosphate. IP3 is a second messenger that releases Ca2+ from the dense tubular system to the cytosol in stimulated platelets. Our present information indicates that [3H]IP3 is dephosphorylated to [3H]inositol bisphosphate (IP2) and [3H]inositol monophosphate (IP) by human platelets treated with 0.05-0.10% Triton X-100. This dephosphorylation of [3H]IP3 to [3H]IP2 and [3H]IP is also observed when platelets are permeabilized by electrical stimulation or by 20 micrograms/ml saponin. These detergents or electropermeabilization allow IP3 to access cytosolic IP3 phosphatase. Pretreatment of intact platelets with phorbol dibutyrate and 1-oleyl-2-acetyldiacylglycerol for 30 s, at concentrations that maximally activate protein kinase C, stimulates the conversion of IP3 to IP2 and IP. This suggests a role for protein kinase C in the regulation of IP3 degradation.