Fluorescent and biotinylated probes for B2 bradykinin receptors:: Agonists and antagonists

Peptide ligands carrying additional reporter groups are valuable research tools to facilitate biochemical and pharmacological studies of G protein-coupled receptors. B-2 bradykinin receptors, widely distributed in mammalian tissues, regulate many physiological systems and are therapeutic targets. Acylation of the amino-terminus of bradykinin (BK) and a B-2a-selective antagonist produced ligands derivatized with biotinamidocaproate or 7-Amino-4-methylcoumarin-3-acetate. These fluorescent and biotinylated peptides bound with high affinity to bovine and rodent B-2 receptors. Analysis of second messenger production confirmed that fluorescent and biotinylated analogs of BK 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 these selective receptor probes will be useful in studying B-2 receptor localization, expression and desensitization. (C) 1999 Elsevier Science Inc. All rights reserved.