97 research outputs found
Aspirin-triggered 15-Epi-Lipoxin A4 (LXA4) and LXA4 Stable Analogues Are Potent Inhibitors of Acute Inflammation: Evidence for Anti-inflammatory Receptors
Mechanisms in anti-inflammation and resolution: the role of lipoxins and aspirin-triggered lipoxins
High affinity [3H]formoterol binding sites in lung: Characterization and autoradiographic mapping
Agonist binding to the β2-adrenoceptors and its mapping were studied using the newly developed radioligand [3H]formoterol. The results of [3H]formoterol saturation binding and formoterol inhibition of [3H]formoterol binding were consistent with binding to a single class of receptors (K(d) = 1.34 ± 0.15 nM, B(max) = 154.9 ± 8.0 fmol/mg protein in guinea pig lung membranes, n = 8; K(d) = 1.05 ± 0.17 nM, B(max) = 67.8 ± 8.1 fmol/mg protein in human lung membranes, n = 5) and competition assays with other agonists and antagonists disclosed only a single class of site. The nonhydrolyzable GTP analogue GTPγS caused a reduction in both K(d) and B(max), indicating that the receptors labelled by [3H]formoterol are coupled to a guanine nucleotide binding regulatory protein. Receptor mapping of [3H]formoterol binding sites shows that β2-adrenoceptors were widely distributed in both guinea pig and human lung, with dense labelling over airway epithelium and uniformly over alveolar walls, and sparse labelling of airway and vascular smooth muscle. In addition, submucosal glands were also sparsely labelled in human bronchus. The distribution of β2-adrenoceptors was similar to the pattern previously described with non-selective radiolabelled antagonists in the presence of selective β1-adrenoceptor antagonists.link_to_subscribed_fulltex
Modulation of airway smooth muscle β-adrenoceptor function by a muscarinic agonist
We have investigated the effect of a muscarinic agonist and protein kinase C (PKC) activation on β-adrenoceptors and their coupling to adenylyl cyclase in bovine tracheal smooth muscle. There was a significant reduction in maximum binding capacity of [125I]iodocyanopindolol ([125I]ICYP) after exposure to carbachol and 4β-phorbol 12β-myristate 13α-acetate (PMA). Similarly both carbachol and PMA inhibited the 5'-guanylylimidodiphosphate-induced shift in [125I]ICYP binding by isoproterenol and significantly decreased isoproterenol-induced cyclic AMP accumulation. A phorbol ester, 4α-phorbol 12,13-didecanoate which does not activate PKC had no effect on β-receptor binding or coupling. These results suggest that PKC activation directly via a phorbol ester and indirectly via muscarinic receptor stimulation may lead to reduction and uncoupling of β-receptors in airway smooth muscle. We suggest that this mechanism may be relevant to the reduction in β-receptor coupling in asthmatic airways as an effect of PKC activation by inflammatory mediators and neurotransmitters.link_to_subscribed_fulltex
Astrocytic insulin‐like growth factor‐1 prevents excitotoxic downregulation of adenosine deaminase acting on RNA in calcium dynamics
Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists
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