Potential Participation of calpain in platelet activation studied by use of a cell penetrating calpain inhibitor (Calpeptin)

Journal Article · Sun Dec 31 23:00:00 EST 1989 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(90)90414-M· OSTI ID:7138207

Tsujinaka, Toshimasa; Ariyoshi, Hideo; Uemura, Yoshio; Sakon, Masato; Kambayashi, Junichi; Mori, Takesada ^[1]

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1. Osaka Univ. Medical School, Fukushima (Japan)

Employing a cell penetrating calpain inhibitor (calpeptin), the role of calpain in platelet activation was examined. In washed platelets (WPs) both thrombin and collagen-induced platelet aggregation were dose-dependently inhibited by calpeptin. The addition of plasma to WPs interfered with the action of calpeptin, however more than 3 min preincubation of calpeptin with WPs completely abolished the influence of plasma. In thrombin-activated WPs with calcium, the increase of intracellular calcium concentration, (Ca{sup 2+})i, and the production of inositol triphosphate (IP{sub 3}) were dose-dependently inhibited by calpeptin. The generation of thromboxane B{sub 2} (TxB{sub 2}) was inhibited by calpeptin in collagen and thrombin-activated WPs. In ({sub 3}H)-arachidonic acid (AA)-labelled platelets, calpeptin increased the amount of ({sup 3}H)-AA liberated by inhibiting ({sup 3}H)-AA degradation after collagen or thrombin stimulation. When ({sup 14}C)-AA degradation by the platelet suspension was observed, calpeptin inhibited TxB{sub 2} and hydroxyheptadecatrienoic acid (HHT) generation but increased prostaglandin (PG) E{sub 1}, E{sub 2}, 12-hydroxyeicosatetraenoic acid (12HETE) and AA. Based on these findings, calpain may be involved in the activation phospholipase C and thromboxane synthetase.

• OSTI ID: 7138207
• Journal Information: Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 46:15; ISSN 0024-3205; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ARACHIDONIC ACID
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION
BLOOD PLATELETS
BODY FLUIDS
CALCIUM COMPOUNDS
CARBON 14 COMPOUNDS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
COAGULANTS
COLLAGEN
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
ENZYMES
ESTERASES
FUNCTIONS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPASES
MATERIALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PEPTIDES
PROTEINS
SCLEROPROTEINS
SERINE PROTEINASES
THROMBIN
TRACER TECHNIQUES
TRITIUM COMPOUNDS