Masaki Hagiwara

New potent enkephalin analogs containing trifluoromethylamino acid residues

Abstract A series of new methionine-enkephalin analogs containing trifluoronorvaline (TFNV) or trifluoronorleucine (TFNL) in place of Gly 2 or Gly 3 are synthesized. The new analogs bearing (D)-TFNV in place of Gly 2 exhibit ca. 100,000 times enhancement in in vivo analgesic activity in comparison with methionine-enkephalin. The in vitro binding assays for mu, delta and kappa receptors reveal that this enhancement is not based on the much stronger binding to these receptors, but mainly due to the extremely efficient inhibition of degradation by aminopeptidase(s).

Calcium-Induced Platelet Aggregation in Washed Platelets from Guinea Pigs

The present study investigated the effects of extracellular calcium on washed platelets of guinea pigs, rabbits, rats and humans. CaCl2 without agonists induced platelet aggregation in guinea pigs and rabbits, but not in rats or humans. CaCl2 increased platelet [Ca2+]i in Fura-2-loaded guinea pig platelets. Calcium-induced platelet aggregation was inhibited by W-7 (a calmodulin antagonist), aspirin, indomethacin, TMB-8 (an inhibitor of intracellular Ca2+ release) and also nicardipine (a calcium antagonist). These data suggest that CaCl2-induced platelet aggregation is mediated by calmodulin, cyclooxygenase and other, as yet unknown, mechanisms.