Direct thrombin inhibitors built on the azaphenylalanine scaffold provoke degranulation of mast cells
Peternel, Luka ...
The main structural feature of direct thrombin inhibitor LK-732 responsible for the appropriate interaction at the thrombin active site is a strong basic group.A possibility that a strong basic group ...of LK-732 might contribute to the mast cell degranulation effect and consequent reduction of tracheal air flow (TAF) and fall of mean arterial blood pressure (MAP) in rats was investigated in the present study. At doses up to 5 mgžkg (i.v.), LK-732 did not cause significant changes of TAF and MAP. At 7 mgžkg (i.v.), a sudden reduction of TAF and a fall of MAP was observed within 5 min after LK-732 administration (75% mortality, p=0.007).A less basic direct thrombin inhibitorLK-658 (21 mgž kg, i.v.) did not significantly disturb TAF and MAP.A reduction of TAF and a fall of MAP caused by LK-732 (7 mgžkg,i.v.) was a lomost completely abolished in rats with degranulated mast cells (0% mortality, p=0.008). LK-732 concentration-dependently degranulated rat peritoneal mast cells in vitro (pEC 50=1.92 0.05 M).A structure-activity relationship (SAR) study revealed that the terminal basic groups attached to the aromatic ring are responsible for the mast cell degranulation effect. A good correlation was observed between mast cell degranulation and pKb of analogues of LK-732 (R2 =0.49), but not between mast cell degranulation and thrombin K i (R2 =0.23). LK-732-induced reduction ofTAF, the fall of MAP and high mortality originate from LK- 732-induced mast cell degranulation. As judged by the SAR study, this effect could be overcome by reducing the basicity of LK-732
Bibliografsko gradivo je bilo uspešno dodano na polico.
Dodajanje bibliografskega gradiva na polico ni uspelo.
Gradivo je že na polici.
Trajna povezava
URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto
Faktor vpliva
Izdaja
Kategorija
Razvrstitev
JCR
SNIP
JCR
SNIP
JCR
SNIP
JCR
SNIP
Izberite knjižnično izkaznico:
Baze podatkov,
v katerih je revija indeksirana
Ime baze podatkov
Področje
Leto
Povezave do osebnih bibliografij avtorjev
Povezave do podatkov o raziskovalcih v sistemu SICRIS
Storitev za pridobivanje naslova trenutno ni dostopna, prosimo, poskusite še enkrat.
S klikom na gumb "V redu" boste potrdili zgoraj izbrano prevzemno mesto in dokončali postopek rezervacije.
S klikom na gumb "V redu" boste potrdili zgoraj izbrano prevzemno mesto in naslov za dostavo ter dokončali postopek rezervacije.
S klikom na gumb "V redu" boste potrdili zgoraj izbrani naslov za dostavo in dokončali postopek rezervacije.
Obvestilo
Trenutno je storitev za avtomatsko prijavo in rezervacijo nedostopna. Gradivo lahko rezervirate sami na portalu Biblos ali ponovno poskusite tukaj kasneje.
Citiranje
Funkcionalnost trenutno ni na voljo. Prosimo, poskusite kasneje.
