Characterisation of the beta adrenergic response cascade in fetal guinea pig lung.

Abstract

Background -Suitable models for the study of lung development are needed. The suitability of the guinea pig for studying the role of the P adrenergic response cascade in fetal lung development has been evaluated. Methods -Radioligand binding assays with iodine-125 labelled iodopindolol were performed to identify and characterise the adrenergic receptors. To demonstrate that these receptors were functional, isoprenaline and forskolin stimulated generation of cyclic AMP (cAMP) in the lung tissue was quantitated by radioimmunoassay. would be a more suitable animal model for several reasons. Firstly, the guinea pig has a longer gestation (67-69 days) than rabbits and rats and is also relatively mature at the time of delivery.4 Secondly, the proportion of time spent in the different stages of morphological maturation of the lung and the timing of these stages in relation to delivery in the guinea pig5 are more similar to those in the human than those in the other small mammals. For example, the saccular stage of lung development begins by 50 days (75% of gestation) in the guinea pig5 and by 28 weeks (70% of gestation) in the human fetus,6 whereas the rabbit and rat only reach the saccular stage by 90-95% of gestation.7 In addition, in both the guinea pig8 and the human6 alveolarisation of the lung is well established before term, and surfactant synthesis9 and induction of antioxidant enzymes'0 occur relatively late in gestation in both. The purpose of this study was to characterise 1 adrenergic responses in fetal guinea pig lung in order to assess the appropriateness of this model to study the involvement of the ,B adrenergic response cascade in lung development. Results