Fluorescent and biotinylated probes for B-2 bradykinin receptors: Agonistsand antagonists

Peptide ligands carrying additional reporter groups are valuable research t ools to facilitate biochemical and pharmacological studies of G protein-cou pled receptors. B-2 bradykinin receptors, widely distributed in mammalian t issues, regulate many physiological systems and are therapeutic targets. Ac ylation of the amino-terminus of bradykinin (BK) and a B-2a-selective antag onist produced ligands derivatized with biotinamidocaproate or 7-Amino-4-me thylcoumarin-3-acetate. These fluorescent and biotinylated peptides bound w ith high affinity to bovine and rodent B-2 receptors. Analysis of second me ssenger production confirmed that fluorescent and biotinylated analogs of B K were B-2 receptor agonists whereas derivatives of DArg(0)[Hyp(3),DPhe(7), Leu(8)]BK were BK receptor antagonists. The complimentary properties of the se selective receptor probes will be useful in studying B-2 receptor locali zation, expression and desensitization. (C) 1999 Elsevier Science Inc. All rights reserved.