β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, t...

Objective: We recently reported the hyper-responsiveness of human skeletal muscle resistance arteries (SkMRAs) to noradrenaline in critical limb ischaemia (CLI). In this study we investigated the characteristics of a -adrenoceptor subtypes and evaluated the agonist 1 affinity and adrenoceptor reserve in the ischaemic arteries. Methods: Human SkMRAs were isolated from non-ischaemic and ischaemic...

BACKGROUND AND PURPOSE Oestrogen confers cardioprotection by down-regulating the beta(1)-adrenoceptor and suppressing the expression and activity of protein kinase A. We hypothesized that oestrogen may also protect the heart by suppressing Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), another signalling messenger activated by the beta(1)-adrenoceptor, that enhances apoptosis. EXPERI...

BACKGROUND It is well known that during cardiopulmonary bypass (CPB) with cardioplegic cardiac arrest, catecholamines are vigorously increased. We therefore investigated whether this might cause desensitization of human cardiac beta-adrenoceptors. METHODS AND RESULTS We assessed in 12 children with acyanotic congenital heart disease who underwent open-heart surgery right atrial beta-adrenocep...

In vitro studies suggest that glucocorticoids may counteract beta-agonist-induced desensitization of beta-adrenoceptors by actions at the transcriptional level, but the clinical relevance of such findings is not clear. Oral terbutaline treatment decreases beta-adrenoceptor sensitivity in alveolar macrophages in vivo. This effect is not counteracted by inhaled or orally taken steroids. We theref...

We examined the down-regulation of alpha-1B adrenoceptors in Madin-Darby canine kidney D1 (MDCK) cells with an emphasis on a possible role of protein kinase C. The alpha-1 adrenoceptor agonist phenylephrine (1-100 microM) concentration-dependently down-regulated alpha-1B adrenoceptors in MDCK cells. Down-regulation by 100 microM phenylephrine was detectable after 2 hr and maximal after 8 to 24 ...

The aim of this study was to systematically compare the interaction of the long-acting beta2-adrenoceptor agonists formoterol and salmeterol with short-acting beta2-adrenoceptor agonists in contracted human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Formoterol or salmeterol at concentrations inducing up to 92 and 94% of their maximal relaxant effect, res...