Modulation of mast cell activity by a peptide agonist of the thrombin receptor: role of nitric oxide.
The effect of a thrombin receptor agonist peptide (TRAP-6) on the release of nitric oxide (NO) and platelet activating factor (PAF) from resting and calcium-ionophore (A23187)-activated rat peritoneal mast cells (RPMC) was studied using a platelet aggregation bioassay. RPMC spontaneously released NO, which inhibited TRAP-6-, ADP-, and PAF-stimulated platelet aggregation. This effect of NO was abolished by the addition of an NO binding agent, oxyhemoglobin (oxyHb), to the platelet suspension. The RPMC-induced suppression of platelet aggregation was completely inhibited by the NO-synthase inhibitor L-NAME. TRAP-6 and its high affinity analog haTRAP stimulated the rapid release of NO from RPMC. The effect of TRAP-6 was inhibited by pretreatment of the RPMC with L-NAME or with the inhibitor of the constitutive NO-synthase isoform (cNOS) calmidazolium. TRAP-6 inhibited PAF release from A23187-activated RPMC via an NO-dependent mechanism. Platelet aggregation induced by PAF release from activated RPMC was also confirmed in experiments using the PAF receptor antagonist ginkgolide B. Thus, TRAP-6 is a rapidly acting modulator of mast cell reactivity; it stimulates NO release and inhibits PAF secretion.
Strukova
S M
SM
Department of Human and Animal Physiology, School of Biology, Lomonosov Moscow State University, Moscow, 119899, Russia.
Chistov
I V
IV
Umarova
B A
BA
Dugina
T N
TN
Storozhevykh
T P
TP
Pinelis
V G
VG
Glusa
E
E
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D007249:Inflammation; D008407:Mast Cells / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010537:Peritoneum / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D018179:Receptors, Thrombin / Q000819:agonists*; D013917:Thrombin / Q000502:physiology
D010446:Peptide Fragments; D010972:Platelet Activating Factor; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D009569:Nitric Oxide; D000001:Calcimycin; D013917:Thrombin