Agonist-independent alteration in beta-adrenoceptor-G-protein-adenylate cyclase system in an equine model of recurrent airway obstruction.

We examined the inhibitory sympathetic beta-adrenergic mechanisms in peripheral lung, bronchi and trachea of an equine model of recurrent airway obstruction (RAO), to support the hypothesis that the beta-adrenergic receptor dysfunction is not only restricted to cell surface receptor density but rather encompasses a mechanistic defect apart from the receptor, to the intracellular signaling components. The non-asthmatic lung possessed 3.2-fold more beta-adrenergic receptors than bronchi (496 +/- 19.

Pharmacological and biochemical characterization of the beta-adrenergic signal transduction pathway in different segments of the respiratory tract.

Although in the respiratory system there is great therapeutic interest in manipulating and understanding the beta-adrenoceptor-G-protein-adenylate cyclase (AC) signal transduction pathway, little is known on segmental differences among lung, bronchus, and trachea with regard to the receptor concentration and interaction to G-proteins and coupling to AC. In this study, patterns of distribution and absolute quantities of beta-adrenoceptor subtypes beta(1) and beta(2) were determined in membranes of equine lung parenchyma, bronchial and tracheal epithelium with the underlying smooth muscle by saturation and competition binding assays using the radioligand (-)-[125I]-iodocyanopindolol (ICYP). Additionally, the functional coupling of beta-adrenoceptors to G-proteins (assessed by beta-agonist competition binding in the presence and absence of GTP) as well as the coupling efficiency and biochemical activities of AC was investigated in each region.