Wc studied the role of non.selecttv© tyi~ (ET.) of ¢ndothelin (ET} receptor in the vaseulature, using a ligand specific to the fiT. receptor) [Olu~] • sarafotoxin S6b ([Olu'*lgR'rh}. Endothelium.containln8 rat thoracic aorta pos~s~d specific binding sites For ~)l.[OhP]SRTb. which were almost diminatcd by removal ctf the endothelium, while ET.3-sl~cific binding sites were not detected in tl' c endothdium.intaet rat aorl=. Only ET, receptor was deIected in the membranes From the endothdium of porcine thoracic aorta. [GIu'~ISR.Tb exerted only vasodilalion in rat aortic rinB. These findings indicate that El?. receptors are located on vascular endothellum and linked to vasodilation.

No abstract

Epinastine caused an inhibition of histamine release from rat peritoneal mast cells induced by both antigen-antibody reaction and compound 48/80. Epinastine was similarly effective in inhibiting compound 48/80-induced histamine release not only from isolated rat peritoneal mast cells but also from rat mesenterial pieces. Also, histamine release from lung pieces obtained from actively sensitized guinea pigs after exposure to antigen challenge was markedly inhibited by epinastine. The drug was effective in inhibiting not only Ca2+ uptake into lung mast cells in actively sensitized guinea pigs but also Ca2+ release from the intracellular Ca store of rat peritoneal mast cells exposed to both compound 48/80 and substance P. No significant changes were observed in phosphodiesterase activity in rat peritoneal mast cells treated with epinastine, while adenylate cyclase activity was augmented by epinastine. Epinastine has no inhibitory effect on histamine release induced by Ca2+ or IP3 from permeabilized mast cells. However, the drug significantly and dose-dependently suppressed calmodulin activity suggesting that histamine release inhibition due to epinastine may be partly attributable to Ca(2+)-calmodulin dependent process(es). The drug caused no visible changes in thermodynamic behavior of lipids, either in order parameter or in differential scanning calorimetry, indicating that the drug has no influence on membrane fluidity.

No abstract

Sarafotoxins (SRTa, SRTb and SRTc) as well as endothelin-1 (ET-l) produced vasoconstrictions in rat thoracic aorta, rat isolated perfused mesentery and pithed rat in various of extents. The potency was ET-l > SRTb > SRTa > SRTc at lower doses, but SRTb > ET-I > SRTa > SRTc at higher doses. [Nitrophenylsulfenylated Tt@r]SRTb and SRTb(l-19) caused no vasoconstriction. Either the reduction and carboxymethylation of Cys residues, the destruction of the intramolecular loop or the production of the non-natural disulfide bond, eliminated the constrictor activity. These results indicate that TrpZr and the intramolecular loop structure are essential, and Lys9 and Tyr*" may play some important roles for the vasoconstrictor activity of these peptides.