Species variability in platelet and other cellular responsiveness to thrombin receptor-derived peptides.
The aggregation of platelets from a variety of animal species in response to thrombin receptor-derived activating peptides was evaluated. A series of 14-(SFLLRNPNDKYEPF), 7-(SFLLRNP-NH2), 6-(SFLLRN-HN2) or 5-(SFLLR-NH2) residue peptides, the structures of which were based on the deduced amino acid sequence of the human thrombin receptor, promoted full aggregation of platelets in plasma from humans, African Green and Rhesus monkeys, baboons and guinea pigs at 4-50 microM depending on the peptide used. Platelets in plasma from rabbit, dog, pig, and hamster underwent a shape change but failed to aggregate in response to these peptides over 3 log units of peptide up to 800 microM, despite being fully responsive to human thrombin. However, because the receptor peptides induced shape change in the platelets from these non-aggregating species, they apparently can activate some of the intracellular signaling system(s) usually initiated by thrombin in these platelets. In contrast, platelets from rats did not undergo shape change or aggregate in response to the peptides. A 7-residue receptor-derived peptide based on the deduced amino acid sequence of the clone of the hamster thrombin receptor (SFFLRNP-N2) was nearly as efficacious as the corresponding human receptor-derived 7-residue peptide to promote aggregation of human platelets. However, the hamster peptide could not promote aggregation of hamster platelets in plasma at up to 800 microM peptide, while a shape change response was elicited. Platelets from rats, rabbits and pigs also did not aggregate in response to this peptide derived from the hamster thrombin receptor, but all species except the rat underwent a shape change.(ABSTRACT TRUNCATED AT 250 WORDS)
Connolly
T M
TM
Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486.
Condra
C
C
Feng
D M
DM
Cook
J J
JJ
Stranieri
M T
MT
Reilly
C F
CF
Nutt
R F
RF
Gould
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000648:ultrastructure; D002460:Cell Line; D006224:Cricetinae; D004261:DNA Replication / Q000187:drug effects; D004285:Dogs / Q000097:blood; D005347:Fibroblasts / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008322:Mammals / Q000097:blood*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011323:Primates / Q000097:blood; D051381:Rats; D018179:Receptors, Thrombin / Q000737:chemistry / Q000502:physiology*; D012377:Rodentia / Q000097:blood; D013045:Species Specificity; D013552:Swine / Q000097:blood
D010446:Peptide Fragments; D018179:Receptors, Thrombin