Background and aims—The subtype and species related heterogeneity of â adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. Methods—Relaxation of muscle strips was measured in vitro. Results—The following agonists had decreasing relaxing potency (eVective concentration range 10–10 mol/l): (−)isoprenaline (non-selective), terbutali...

Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, is characterized by a progressive decline of the cognitive functions, in particular a loss of memory, learning and attention, and it does not have a simple etiology. Most of the cases are sporadic and the factors involved are unknown. A very small percentage of cases are hereditary and are due to mutations in one of the thr...

The excessive use of â2 agonists has been associated with increased asthma mortality, although this seems to be due to confounding by disease severity rather than direct drug toxicity. 2 Dose-response studies in stable asthmatics have shown the potential for high doses of salbutamol to produce direct or indirect cardiovascular sequelae mediated by extrapulmonary â2 adrenoceptor stimulation incl...

Background—In vitro the long acting â2 agonist salmeterol can, in contrast to formoterol, behave as a partial agonist and become a partial antagonist to other â2 agonists. To study this in vivo, the bronchodilating eVect of salbutamol was measured during methacholine induced moderate to severe bronchoconstriction in patients receiving maintenance treatment with high dose long acting â2 agonists...

Background—Polymorphisms of the â2 adrenoceptor influence receptor function in vitro and asthma phenotypes in vivo. However, their importance in determining responses to inhaled â agonist treatment has not been clearly defined. Methods—In a retrospective analysis of previously published data we have examined relationships between polymorphisms at codons 16 and 27 of the â2 adrenoceptor and clin...

–The GABAA receptor is a ligand-operated chloride channel. It has a pentameric structure. In mammalian brain different subunits are recruited from four gene subfamilies. Using immunocytochemistry, we investigated the distribution of the 13 GABAA receptor subunits in the hippocampus of the rat. GABAA receptor subunits were heterogeneously distributed within different hippocampal subfields. High ...

In this issue of Thorax Blais et al report results from a population based register study which show that first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce by up to 80% the risk of a hospital admission for asthma compared with regular treatment with theophylline. It is a dramatic result, albeit not so surprising. Regular us...

Background—Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear. Animal experiments indicate that the combination of hypoxia and â2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the eVect of hypoxia on the systemic vascular eVects of salbutamol in patients with...

The method of graded contractions, based on the preservation of the automorphisms of finite order, is applied to the affine Kac-Moody algebras and their representations, to yield a new class of infinite dimensional Lie algebras and representations. After the introduction of the horizontal and vertical gradings, and the algorithm to find the horizontal toroidal gradings, I discuss some general p...