Biologic activities of iodinated analogues of Tyr0-bradykinin and bradykinin-Ile10-Tyr11 assessed in the rat uterus and the guinea pig ileum.
1. The biological activity of bradykinin (BK) and analogues containing ofr in extended N- or C-terminal portions of the molecule, as well as that of their iodinated products, was compared in isolated rat uterus and guinea pig ileum preparations. 2. BK-Tyr10 and BK-Ile10-Tyr11 were obtained by solid phase synthesis employing fmoc chemistry. 3. Iodination of BK-Ile10-Tyr11 and Tyr0-BK was performed using iodobeads, and the products were purified by reverse-phase HPLC. 4. The relative potency (RP) of noniodinated analogues in the uterus was: Tyr0-BK (1.3) = BK (1.0) > BK-Ile10-Tyr11 (0.45) > > BK-Tyr10 (0.02) and BK (1.0) > BK-Ile10-Tyr11 (0.25) = Tyr0-BK (0.22) > > > BK-Tyr10 (0.002). The RP of mono-iodo (MI) and di-iodo (DI) products was: BK (1.0) > DI-BK-Ile10-Tyr11 (0.63) = DI-Tyr0-BK (0.63) > MI-Tyr0-BK (0.46) = MI-BK-Ile10-Tyr11 (0.40). 5. The RP of noniodinated analogues in the guinea pig ileum was: BK (1.0) > MI-Tyr0-BK (0.39) > MI-BK-Ile10-Tyr11 (0.17) = DI-Tyr0-BK (0.16) = DI-BK-Ile10-Tyr11 (0.13). 6. Differences in RP of 8-10 fold for Tyr0-BK or BK-Tyr10 and 2-fold for BK-Ile10-Tyr11 were observed between the two preparations used, indicating possible receptor differences. 7. Iodination caused a reduction in the RP of the analogues in both preparations. 8. In the rat uterus, the changes in the RP of the Tyr0-BK analogues were more evident than those observed with the iodinated analogues of BK-Ile10-Tyr11, indicating that iodination causes different changes in RP, according to the localization of the Tyr in the molecule. 9. The data support the idea that iodinated analogues of BK-Ile10-Tyr11, with intact N-terminal portion, may be as useful as iodinated analogues of Tyr0-BK for the study of BK receptors.
Cunha
V
V
Department of Pharmacology, School of Medicine of Ribeiráo Preto, University of Sáo Paulo, Brazil. fmdacorr@fmrp.ups.br
Gutierrez
J
J
Corrêa
F M
FM
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*
D000596:Amino Acids; C103293:bradykinin, Ile(10)-Tyr(11)-; C026201:bradykinin, Tyr-; D001920:Bradykinin