1. Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP9α
- Author
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Sylvia Mueller, Inge Paegelow, Wolf-Dieter Siems, Gabriele Vietinghoff, Siegmund Reissmann, and Rita Gothe
- Subjects
ED, effective dose ,Receptor, Bradykinin B2 ,Physiology ,Boc, tert-butyloxycarbonyl ,AA, arachidonic acid ,Angiotensin-Converting Enzyme Inhibitors ,BPA, p-benzoylphenylalanine ,Pharmacology ,DMF, N,N-dimethylformamide ,Biochemistry ,ABA, 4-azidobenzoic acid ,DIEA, diisopropylethylamine ,chemistry.chemical_compound ,Endocrinology ,Radioligand binding ,BPP9α, bradykinin potentiating peptide 9α (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) ,Aloc, allyl oxycarbonyl ,BKR-B1, bradykinin B1 receptor ,Chlorocebus aethiops ,Phosphoprotein Phosphatases ,Inositol phosphate ,Receptor ,Ddz, α,α-dimethyl-3,5-dimethoxy-benzyloxycarbonyl ,HOAt, 1-hydroxy-7-azabenzotriazole ,Trt, triphenylmethyl ,HOCr, hydroxycrotonic acid ,Potentiation ,chemistry.chemical_classification ,DEAE, diethylaminoethyl ,DMEM, Dulbecco's modified Eagle's medium ,Fmoc, 9-fluorenylmethyl oxycarbonyl ,Mtr, methoxytrimethylbenzene sulphonyl ,Chemotaxis ,Long-term potentiation ,Drug Synergism ,Smooth muscle contraction ,DIC, diisopropylcarbodiimide ,Angiotensin I-converting enzyme ,DTE, dithioerithritol ,DCM, dichloromethane ,Arachidonic acid ,COS Cells ,Dde, N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl ,IPn, inositol phosphates ,BK, bradykinin ,PMN, polymorphonuclear leukocytes (neutrophils) ,Calyculin ,Muscle Contraction ,Signal Transduction ,Bradykinin potentiating peptide ,DMSO, dimethylsulfoxide ,IP3, inositol 1,4,5-trisphosphate ,J527, Pro-Trp-Pro-Lys-Pro-Gln-Ile-Pro-Pro ,Ca2+-influx ,Polymorphonuclear leukocytes ,Inositol Phosphates ,Guinea Pigs ,Molecular Sequence Data ,Bradykinin ,Peptidyl-Dipeptidase A ,Article ,TFA, trifluoroacetic acid ,Cellular and Molecular Neuroscience ,MEM, Eagle's minimal essential medium ,BOP, benzotriazole-1-yl-oxy-tris (dimethylamino) phosphonium hexafluorophosphate ,Protein phosphatases ,Animals ,Humans ,Amino Acid Sequence ,Teprotide ,Bradykinin receptor ,Ram, ramiprilat ,FR190997, 8-[2,6-dichloro-3-[N-(E)-4-(N-methylcarbamoyl)cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridyl-methoxy)quinoline ,J526, Pyr-Trp-Pro-Lys(ASA)-Pro-Gln-Ile-Pro-Pro ,ɛAbu(ßPhe), erythro-α-amino-ß-phenyl-butyric acid ,BPP, bradykinin potentiating peptide ,Muscle, Smooth ,TBTU, 2-(1H-benzotriazol-1-yl)1,1,3,3-tetramethylguanidinium tetrafluoroborate ,ACE, angiotensin I-converting enzyme ,HOBt, 1-hydroxybenzotriazole ,BKR, bradykinin receptor ,chemistry ,ASA, 4-azidosalicylic acid ,J725, DArg-Arg-Pro-Hyp-Gly-Thi-Ser-Pro-ɛAbu(ßPh)-Arg ,GPI, guinea pig ileum ,BKR-B2, bradykinin B2 receptor ,HYCRAM, hydroxycrotonyl amidomethyl linker ,Calcium ,Pd0, palladium tetrakis triphenylphosphine ,Peptides ,HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylguanidinium hexafluorophosphate - Abstract
Synthetic analogues of the bradykinin potentiating nonapeptide BPP 9α indicate significantly different structural requirements for potentiation of the bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of isolated somatic angiotensin I-converting enzyme (ACE). The results disprove the ACE inhibition as the only single mechanism and also the direct interaction of potentiating peptides with the bradykinin receptors in transfected COS-7 cells as molecular mechanism of potentiation. Our results indicate a stimulation of inositol phosphates (IP n ) formation independently from the B 2 receptor. Furthermore, the results with La 3+ support the role of extracellular Ca 2+ and its influx through corresponding channels. The missing effect of calyculin on the GPI disproves the role of phosphatases in the potentiating action. These experimental studies should not only contribute to a better understanding of the potentiating mechanisms but also incorporate a shift in the research towards the immune system, in particular towards the immunocompetent polymorphonuclear leukocytes. The chemotaxis of these cells can be potentiated most likely by exclusive inhibition of the enzymatic degradation of bradykinin. Thus the obtained results give evidence that the potentiation of the bradykinin action can occur by different mechanisms, depending on the system and on the applied potentiating factor.
- Published
- 2005