New bradykinin analogs in contraction of rat uterus.
In this study, we evaluated 20 of our previously synthesized peptides on isolated rat uterus by Holton's procedure with minor modifications, and compared their activity with that assessed previously by their ability to inhibit vasodepressor response to exogenous bradykinin (BK) in conscious rats. We used [D-Arg(0), Hyp(3), Thi(5, 8), (D-Phe)(7)]BK, the B(2) antagonist of Vavrek and Stewart as a model when designing our analogs. We observed that, in the case of the rat uterus test, the activity of peptides modified by acylation of the N-terminus with various bulky groups depends substantially on the chemical character of the substituent. We also learned that, contrary to previous examples, acylation of the N-terminus of antagonists, which contain a sterically restricted fragment in the C-terminal part, may not improve their antagonistic potencies. Besides an improved characterization of a series BK analogs, our studies have provided new information on the structure-activity relationship, which in turn may be of value in the design of more potent and selective bradykinin antagonists. The results of our studies appear to support the hypothesis of others about the presence of different subtypes of B(2) receptors in rat uterus and blood vessels.
Trzeciak
H I
HI
Department of Pharmacology, Silesian Medical University, 40-752, Katowice, Poland.
Kozik
W
W
Melhem
S
S
Kania
A
A
Dobrowolski
D
D
Prahl
A
A
Derdowska
I
I
Lammek
B
B
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D010120:Oxytocics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D013329:Structure-Activity Relationship; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D010120:Oxytocics; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D015149:Tocolytic Agents; D014662:Vasoconstrictor Agents; D001920:Bradykinin