Disparate effects of thrombin receptor activating peptide on platelets and peripheral vasculature in rats.
The hemodynamic and platelet effects of the thrombin receptor activating peptide SFLLRN (TRAP) were evaluated in rats. TRAP failed to aggregate rat platelets in vitro (platelet rich plasma) or in vivo in the pulmonary microcirculation. In contrast, TRAP aggregated washed human platelets. Intravenous injection of TRAP (1 mg/kg) in inactin-anesthetized rats produced a biphasic response in blood pressure characterized by an initial depressor response (-25 +/- 3 mmHg for 15-30 s) followed by a pronounced pressor response (50 +/- 7 mmHg for 2-3 min). This increase in blood pressure can be attributed to increases in total peripheral resistance since cardiac output remained unchanged. Further, only the pressor responses were observed in pithed rats suggesting a direct effect of TRAP in causing smooth muscle contraction. Consequently, rat platelets differ from human platelets in that they are resistant to TRAP whereas rat vasculature is highly sensitive to TRAP. These observations suggest that while the thrombin receptors on rat vasculature may be similar to those on human platelets, the receptors and/or the coupling mechanisms in rat platelets appear different from human platelets.
CNS/CV Biological Research, Schering-Plough Research Institute, Kenilworth, NJ 07033-0530, USA.
M S
MS
Chintala
P J
PJ
Chiu
V
V
Bernadino
G G
GG
Tetzloff
R
R
Tedesco
C
C
Sabin
R W
RW
Watkins
E J
EJ
Sybertz
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010974:Platelet Aggregation; D051381:Rats; D013268:Stimulation, Chemical
D010446:Peptide Fragments; C082835:thrombin receptor peptide (42-47)