No abstract

1 We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2 Forskolin (3 nm to 1 pM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC5o was 7.22+0.12M and maximum inhibition was 100 + 0.01%). However, forskolin (<1 pM) did not alter the contraction induced by substance P (SP, 1 pM). 3 Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100+0.01%) without significant effect on SP (1 pM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4 Both the f2-adrenoceptor agonist, procaterol (0.1 nm to 3 nM) and theophylline (100 nm to mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP(1 pM)-induced contractions.5 In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 pM). 6 These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.

Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). However, not all smokers develop clinically significant symptoms. It is recognized that multiple genetic factors and genotype-byenvironment interactions are involved in the development of COPD. Remarkable progress in the genetic knowledge and technology has changed the approaches used to identify candidate genes. Genome-wide linkage analyses have revealed several chromosomal regions linked to COPD phenotypes. The recently introduced gene expression profiling techniques have identified hundreds of genes differentially expressed in COPD. Case-control association studies have reported more than 30 polymorphisms related to the susceptibility to COPD. However, the replication of these results has been limited. In this review, we present our current understanding of the genetic basis of COPD and the findings of genetic studies. The advantages and limitations of the different genetic approaches are also discussed. The increasing knowledge of the COPD genetics combined with a better understanding of its clinical and pathological heterogeneity will have a great potential to change views on the pathogenesis and diagnosis, and even to influence the clinical management.

No abstract

No abstract