BIOLOGIC ACTIVITIES OF IODINATED ANALOGS OF TYR(0)-BRADYKININ AND BRADYKININ-ILE(10)-TYR(11) ASSESSED IN THE RAT UTERUS AND THE GUINEA-PIG ILEUM

1. The biological activity of bradykinin (BK) and analogues containing Tyr 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-Tyr(10) and BK-Ile(10)-Tyr(1 1) were obtained by solid phase synthesis employing fmoc chemistry. 3. Iodination of BK-Ile(10)-Tyr(11) and Tyr(0)-BK was performed using io dobeads(R), and the products were purified by reverse-phase HPLC. 4. T he relative potency (RP) of noniodinated analogues in the uterus was: Tyr(0)-BK (13)=BK (1.O)>BK-Ile(10)-Tyr(11) (0.45)>>BK-Tyr(10) (0.02) a nd BK (1.O)>BK-ILe(10) -Tyr(11) (0.25)=Tyr(0)-BK (0.22)>>>BK-Tyr(10) ( 0.002). The RP of mono-iodo (MT) and di-iodo (DI) products was: BK (1. O)>DI-BK-Ile(10)-Tyr(11) (0.63)=DI-Tyr(0)-BK (0.63)>MI-Tyr(0)-BK (0.46 )=MI-BK-Ile(10)-Tyr(11) (0.40). 5. The RP of noniodinated analogues in the guinea pig ileum was: BK (1.O)>ML-Tyr(0)-BK (0.39)>MI-BK-Ile(10)- Tyr(11) (0.17)=DI-Tyr(0)-BK (0.16)=DI-BK-Ile(10)-Tyr(11) (0.13). 6. Di fferences in RP of 8-10 fold for Tyr(0)-BK or BK-Tyr(10) and 2-fold fo r BK-Ile(10)-Tyr(11) were observed between the two preparations used, indicating possible receptor differences. 7. Iodination caused a reduc tion in the RP of the analogues in both preparations. 8. In the rat ut erus, the changes in the RP of the Tyr(0)-BK analogues were more evide nt than those observed with the iodinated analogues of BK-Ile(10)-Tyr( 11), indicating that iodination causes different changes in RP, accord ing to the localization of the Tyr in the molecule. 9. The data suppor t the idea that iodinated analogues of BK-Ile(10)-Tyr(11), with intact N-terminal portion, may be as useful as iodinated analogues of Tyr-(0 )-BK for the study of BK receptors.