TY - JOUR
T1 - Pharmacological characterization of ligand-receptor interactions at the zebrafish bradykinin receptor
AU - Bromée, Torun
AU - Kukkonen, Jyrki P.
AU - Andersson, Per
AU - Conlon, J. Michael
AU - Larhammar, Dan
PY - 2005/1
Y1 - 2005/1
N2 - Ligand interactions of a piscine bradykinin (BK) receptor expressed in vitro have been characterized for the first time by measuring inositol phosphate accumulation. The ligands were analogues of zebrafish BK with serial substitutions by D-amino acids or alanine. Substitutions at residues Arg 1, Gly 4, Ser 6, Pro 7, Leu 8 and Arg 9 caused greatly reduced potency and maximum response. The Pro 3→Ala analogue had higher potency but lower maximum response. The peptide HOE140 was a weak partial agonist although it is an antagonist at the human B2 receptor and a potent agonist at chicken B2. Thus, cloned zebrafish BK receptor reveals a ligand-interaction profile that is distinct from mammalian B1 and B2 receptors and from the previously characterized BK receptor in trout stomach, but similar to the receptor in cod intestine. These results increase our understanding of the evolution of BK receptors and the functions of the kallikrein-kinin system.
AB - Ligand interactions of a piscine bradykinin (BK) receptor expressed in vitro have been characterized for the first time by measuring inositol phosphate accumulation. The ligands were analogues of zebrafish BK with serial substitutions by D-amino acids or alanine. Substitutions at residues Arg 1, Gly 4, Ser 6, Pro 7, Leu 8 and Arg 9 caused greatly reduced potency and maximum response. The Pro 3→Ala analogue had higher potency but lower maximum response. The peptide HOE140 was a weak partial agonist although it is an antagonist at the human B2 receptor and a potent agonist at chicken B2. Thus, cloned zebrafish BK receptor reveals a ligand-interaction profile that is distinct from mammalian B1 and B2 receptors and from the previously characterized BK receptor in trout stomach, but similar to the receptor in cod intestine. These results increase our understanding of the evolution of BK receptors and the functions of the kallikrein-kinin system.
KW - Alanine substitution
KW - Bradykinin peptide
KW - D-amino-acid substitution
KW - G-protein-coupled recetor
KW - Inositol phosphates
KW - Zebrafish
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U2 - 10.1038/sj.bjp.0706032
DO - 10.1038/sj.bjp.0706032
M3 - Article
C2 - 15644864
AN - SCOPUS:13244274952
SN - 0007-1188
VL - 144
SP - 11
EP - 16
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 1
ER -