M E Lyon1, C A Lefebvre, D J Davis. 1. Department of Pediatrics and Obstetrics/Gynecology, University of Ottawa, Ontario, Canada.
Abstract
BACKGROUND: Suitable models for the study of lung development are needed. The suitability of the guinea pig for studying the role of the beta 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 beta 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. RESULTS: The concentration of beta receptors increased with gestational age from 23 fmol/mg at 35 days to 140 fmol/mg at 64 days. Competition binding studies were consistent with a predominance of beta 2 receptors. The ability of isoprenaline to stimulate cAMP generation was greater during the saccular phase than during the canalicular phase of lung development. Incorporation of tritium labelled choline into phosphatidylcholine increased significantly between the canalicular and saccular phases. CONCLUSIONS: The beta adrenergic response cascade in fetal guinea pig lung exhibits similar characteristics to those previously described in fetal human lung and is therefore a good model in which to study the effects of beta agonists on fetal lung development.
BACKGROUND: Suitable models for the study of lung development are needed. The suitability of the guinea pig for studying the role of the beta 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 beta 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. RESULTS: The concentration of beta receptors increased with gestational age from 23 fmol/mg at 35 days to 140 fmol/mg at 64 days. Competition binding studies were consistent with a predominance of beta 2 receptors. The ability of isoprenaline to stimulate cAMP generation was greater during the saccular phase than during the canalicular phase of lung development. Incorporation of tritium labelled choline into phosphatidylcholine increased significantly between the canalicular and saccular phases. CONCLUSIONS: The beta adrenergic response cascade in fetal guinea pig lung exhibits similar characteristics to those previously described in fetal human lung and is therefore a good model in which to study the effects of beta agonists on fetal lung development.