Effect of Hoe 140, a new B2 noncompetitive antagonist, on guinea pig tracheal bradykinin receptors.
We investigated the effect of the new B2 antagonist D-Arg0[Hyp3,Thi5, D-Tic7, Oic8]bradykinin (BK) (Hoe 140) on the binding of [3H]BK to membranes from guinea pig trachea with respect to the presence of the epithelium. Scatchard analysis of equilibrium data with [3H]BK revealed a single class of binding sites in the epithelium denuded trachea membrane preparation (E-) with a dissociation constant (Kd) of 55 pM and a Bmax of 0.71 fmol.mg tissue-1. When intact trachea (E+) was used, two binding sites were detected: a saturable high-affinity one (Kd of 40 pM and Bmax of 0.69 fmol.mg tissue-1) and a low-affinity one, not really saturable, with a Kd over 180 nM and a Bmax over 18 fmol.mg tissue-1. In guinea pig ileum, a tissue thought to contain B2 receptors, one class of binding sites was detected with a Kd of 209.3 pM and a Bmax of 16.2 fmol.mg tissue-1. In competition experiments ([3H]BK from 0.3 to 0.5 nM), similar results were obtained in (E +/-) and in ileum membrane preparations. B1 ligands did not displace [3H]BK binding, demonstrating the lack of B1 receptors. BK and B2 antagonist, except Hoe 140, fully displaced [3H]BK with Hill coefficients close to the unity. In competition studies only the high-affinity site was labeled by [3H]BK, in the (E+) preparation, as suggested by the inhibition constant value of unlabeled BK. Hoe 140 fully displaced [3H]BK in competition experiments, but with a Hill coefficient significantly less than unity, suggesting the presence of two binding sites for this compound in the three preparations used.(ABSTRACT TRUNCATED AT 250 WORDS)
Trifilieff
A
A
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur Strasbourg I, Illkirch, France.
Da Silva
A
A
Landry
Y
Y
Gies
J P
JP
D000818:Animals; D001665:Binding Sites; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014132:Trachea / Q000187:drug effects*
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C065679:icatibant; D001920:Bradykinin