Two bradykinin binding sites with picomolar affinities.
Bradykinin (BK) and related peptides exert a wide range of effects on several organ systems. We have attempted to sort out these effects by studying the binding interaction of [3H]BK at the membrane level with in vitro receptor binding techniques. High specific activity [3H]BK and an enzyme inhibitor "cocktail" has enabled us to label two BK binding sites with different affinity and peptide specificity in several guinea-pig tissues. In the guinea-pig ileum the high-affinity site has an equilibrium dissociation constant (Kd) for [3H]BK of 13 pM and a maximal number of binding sites of 8.3 pmol/g of tissue wet weight. The low-affinity guinea-pig ileum site displays a Kd of 910 pM, a maximum number of binding sites of 14 pmol/g of tissue wet weight and shows a greater selectivity for BK analogs over Lysyl-BK analogs. Two similar sites can also be discriminated in kidney and heart. The potencies of a series of BK analogs at the high-affinity guinea-pig ileum site correlate well with their potencies in contracting ileal smooth muscle. The binding of [3H]BK in the guinea-pig ileum is inhibited by physiological concentrations of monovalent and divalent cations.
Manning
D C
DC
Vavrek
R
R
Stewart
J M
JM
Snyder
S H
SH
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism; D002412:Cations / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D011282:Pregnenediones / Q000494:pharmacology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014316:Tritium
D002412:Cations; D007457:Iodine Radioisotopes; D011282:Pregnenediones; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D014316:Tritium; C006268:SQ 20811; D001920:Bradykinin