[Hyp3]-bradykinin and [Hyp3]-Lys-bradykinin interact with B2-bradykinin receptors and stimulate inositol phosphate production in cultured human fibroblasts.
The recently isolated, naturally occurring peptide hormones [Hyp3]-bradykinin and [Hyp3]-Lys-bradykinin were investigated for their agonist activity on solubilized binding sites from human fibroblasts. Both ligands competed with [3H]bradykinin binding in a dose-dependent fashion with potencies similar to bradykinin (BK) and Lys-BK. Biological activity was assessed by determination of inositol phosphate accumulation and cyclic 3',5'-adenosine monophosphate synthesis in intact cultured cells. Stimulation by the hydroxylated peptides resulted in a pronounced accumulation of both parameters with similar effectiveness as BK and Lys-BK. These results indicate that [Hyp3]-BK and [Hyp3]-Lys-BK are agonists at the bradykinin receptor system with properties comparable to their non-hydroxylated analogues. This suggests that hydroxylation of kinins does not alter receptor interaction or signal transduction in cultured human fibroblasts.
Dengler
R
R
Kinderklinik im Dr. von Hauner'schen Kinderspital der Universität München, Abteiung für Klinische Biochemie, FRG.
Faussner
A
A
Müller-Esterl
W
W
Roscher
A A
AA
D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007295:Inositol Phosphates / Q000378:metabolism*; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D007295:Inositol Phosphates; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C054550:bradykinin, (hydroxy-Pro)(3)-Lys-; D007609:Kallidin; C021698:bradykinin, hydroxy-Pro(3)-; D000242:Cyclic AMP; D001920:Bradykinin