Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults.
The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor.
Maggio
Nicola
N
Department of Neurobiology, The Weizmann Institute, 76100 Rehovot, Israel.
Shavit
Efrat
E
Chapman
Joab
J
Segal
Menahem
M
D000344:Afferent Pathways / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004827:Epilepsy / Q000503:physiopathology*; D018698:Glutamic Acid / Q000494:pharmacology; D006490:Hemostatics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors
D006490:Hemostatics; C415424:N3-cyclopropyl-7-((4-(1-methylethyl)phenyl)methyl)-7H-pyrrolo(3, 2-f)quinazoline-1,3-diamine; D010446:Peptide Fragments; D011758:Pyrroles; D011799:Quinazolines; C082835:thrombin receptor peptide (42-47); D018698:Glutamic Acid; D013917:Thrombin; D011188:Potassium; D010975:Platelet Aggregation Inhibitors