Collagen-induced secretion-dependent phase of platelet aggregation is inhibited by the snake venom metalloproteinase jararhagin.
Jararhagin, a 52 kDa metalloproteinase from Bothrops jararaca snake venom, belongs to the family of enzymes with an N-terminal Zn2+-containing enzymatic domain, a disintegrin-like domain and a cysteine-rich C-terminal domain. Both jararhagin and jararhagin C, a 28 kDa-protein from the same venom identical to the disintegrin-like domain of jararhagin, inhibit collagen-induced platelet aggregation. In this study, jararhagin and synthetic linear peptides based on the disintegrin-like domain of jararhagin overlapping with the RGD sequence of venom disintegrins, were shown for the first time to inhibit the release of 5-hydroxytryptamine (5-HT) from platelets preloaded with [14C]5-HT and stimulated with collagen. The normal phosphorylation of the 21-kDa myosin light chain (p21) in response to the stimulation indicated that jararhagin and the peptides did not interfere with platelet shape change. The selective inhibition of the secretion-dependent phase of the platelet response to collagen by the enzyme and its peptides was confirmed by the defective phosphorylation of pleckstrin, a 47-kDa platelet protein (p47) involved in dense granule secretion.
Kamiguti
A S
AS
Department of Haematology, University of Liverpool, Royal Liverpool University Hospital, UK.
Moura-da-Silva
A M
AM
Laing
G D
GD
Knapp
T
T
Zuzel
M
M
Crampton
J M
JM
Theakston
R D
RD
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000737:chemistry / Q000494:pharmacology*; D019483:Disintegrins / Q000737:chemistry; D008666:Metalloendopeptidases / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D018994:Myosin Light Chains / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D010750:Phosphoproteins; D010766:Phosphorylation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012701:Serotonin / Q000032:analysis; D000097146:Bothrops jararaca Venom
D001798:Blood Proteins; D003094:Collagen; D003435:Crotalid Venoms; D019483:Disintegrins; D008666:Metalloendopeptidases; D018994:Myosin Light Chains; D010455:Peptides; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D000097146:Bothrops jararaca Venom; C039077:platelet protein P47