Amitraz and its metabolite differentially activate α- and ß-adrenergic-like octopamine receptors.

BACKGROUND: Amitraz is a formamidine acaricide and insecticide used to control ticks, mites and fleas. N2 -(2,4-Dimethylphenyl)-N1 -methyformamidine (DPMF), a metabolite of amitraz, is thought to be an active agent that exerts acaricidal and insecticidal effects by acting as an agonist on octopamine receptors. The emergence of cattle ticks resistant to amitraz is a serious problem that requires urgent attention. The objective of this research was to determine which type of octopamine receptor is the primary target of amitraz and thereby understand the molecular mechanisms of action and resistance to amitraz. RESULTS: Amitraz and DPMF potently activated Bombyx mori α- and ß-adrenergic-like octopamine receptors (α- and ß-AL OARs) that were stably expressed in HEK-293 cells. Notably, DPMF elevated intracellular cAMP levels, with an EC50 of 79.6 pm in ß-AL OARs, the transcripts of which were prevalently and widely localised in B. mori body parts. Furthermore, DPMF elevated the intracellular Ca2+ levels, with an EC50 of 1.17 nm in α-AL OARs. CONCLUSION: Although both amitraz and DPMF acted as OAR agonists, the metabolite DPMF was more potent than amitraz and differentially activated α- and ß-AL OARs. The present findings provide a basis for studies to examine the mechanism of amitraz resistance and to develop novel acaricides and insecticides. © 2016 Society of Chemical Industry.

Changes in lung sounds during asthma progression in a guinea pig model.

BACKGROUND: Lung sound analysis is useful for objectively evaluating airways even in children with asymptomatic asthma. However, the relationship between lung sounds and morphological changes in the airways has not been elucidated. We examined the relationship between lung sounds and chronic morphological changes in the airways during the progression of asthma from onset in guinea pigs. METHODS: Eleven male guinea pigs were examined; of these, seven were used as asthma models and four as controls. The asthma models were sensitized and repeatedly challenged by inhaling albumin chicken egg. We measured lung sounds and lung function twice a week for 21 weeks. After the final antigen challenge, the lungs were excised for histological examination. We measured the ratio of airway wall thickness to the total airway area and the ratio of the internal area to the total airway area in the trachea, third bronchi, and terminal bronchioles. RESULTS: Among the lungs sounds, the difference between the two groups was greatest with respect to inspiratory sound intensity. The ratio of airway wall thickness to the total airway area of the terminal bronchioles was greater in the asthma models than in the controls, and it correlated best with the changes in inspiratory sound intensity in the 501-1000-Hz range (r = 0.76, p < 0.003). CONCLUSIONS: Lung sound intensity in the middle frequency range from 501 to 1000 Hz correlated with peripheral airway wall thickness. Inspiratory sound intensity appeared to be an indicator of morphological changes in small airways in asthma.