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Evidence for a pulmonary B3 bradykinin receptor
S G Farmer1, R M Burch, S A Meeker
1Nova Pharmaceutical Corporation, Baltimore, Maryland 21224-2788.
Molecular Pharmacology
|July 1, 1989
Summary
Bradykinin (Bk) causes bronchoconstriction, but known B1 and B2 receptor antagonists are ineffective. This suggests a novel B3 receptor in pulmonary tissue may mediate these effects, requiring further investigation.
Area of Science:
- Pulmonary pharmacology
- Receptor binding studies
- Respiratory system physiology
Background:
- Bradykinin (Bk) is implicated in pulmonary responses.
- Existing B1 and B2 receptor antagonists show limited efficacy in blocking Bk's effects.
- The precise mechanisms of Bk-induced airway smooth muscle contraction require clarification.
Purpose of the Study:
- To investigate the in vivo and in vitro pulmonary effects of bradykinin (Bk) in guinea pigs.
- To evaluate the inhibitory potential of known Bk B1 and B2 receptor antagonists.
- To identify potential novel receptors involved in Bk-mediated bronchoconstriction.
Main Methods:
- In vivo assessment of Bk-induced bronchoconstriction in guinea pigs.
- In vitro studies using isolated, epithelium-denuded guinea pig trachealis.
- Ligand binding experiments with radiolabeled Bk in guinea pig and ovine airways.
- Testing of various receptor antagonists and agonists.
Main Results:
- Bradykinin (Bk) was a potent bronchoconstrictor in vivo and caused tracheal contractions in vitro.
- Known B1 and B2 receptor antagonists demonstrated weak or no inhibitory effects on Bk-induced responses.
- Ligand binding studies revealed a novel Bk binding site in pulmonary tissue, distinct from B1 and B2 receptors.
Conclusions:
- Pulmonary tissues, especially large airways, possess a novel Bk binding site, potentially a B3 receptor.
- This putative B3 receptor may play a significant role in Bk-induced bronchoconstriction.
- Further research is warranted to characterize this novel receptor and its pharmacological properties.