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Fenoterol treatment and desensitization of beta-adrenoceptors in rabbit foetal lung
1Department of Obstetrics and Gynaecology, University Medical School of Szeged, Hungary.
Abstract:
The foetal lung responds to beta-receptor agonists with a release of surfactant from alveolar cells. The aim of the present study was to investigate whether the administration of the betamimetic fenoterol could influence the desensitization - associated decrease of beta-adrenoreceptors in the rabbit foetal lung. With experiments on pregnant rabbits, this hypothesis was put to the test and found to be true. At a gestational age of 27-28 days, does were infused 7.5-10.0 mg of fenoterol or given Ringer's solution. The does and foetuses were sacrificed at 12 hours from the start of the infusion, and the number and affinity of beta-adrenergic receptors in lung tissues were determined by a direct binding technique using 3H-dihydroprenolol. These studies show that fenoterol can induce desensitization of beta-receptors in the foetal lung but not in the doe. Thus, it is concluded that desensitization of foetal pulmonary adrenoreceptors may result in diminished lung function after long-term treatment with beta-2 sympathicomimetics.
Insights
Fenoterol, a beta-receptor agonist, can cause desensitization of beta-adrenergic receptors in the fetal lung, but not in the adult doe. This may impair fetal lung function with prolonged beta-2 sympathomimetic exposure.
Area of Science:
- Pharmacology
- Pulmonary Medicine
- Developmental Biology
Background:
- Beta-receptor agonists stimulate surfactant release from fetal lung alveolar cells.
- Concerns exist regarding potential desensitization of beta-adrenergic receptors with prolonged agonist exposure.
Purpose of the Study:
- To investigate if fenoterol administration influences beta-adrenergic receptor desensitization in the rabbit fetal lung.
- To determine if fenoterol affects beta-adrenoreceptors in the pregnant doe's lung.
Main Methods:
- Pregnant rabbits (27-28 days gestation) received fenoterol infusion or Ringer's solution.
- Lung tissues from does and fetuses were analyzed 12 hours post-infusion.
- Beta-adrenergic receptor number and affinity were quantified using radioligand binding assays (3H-dihydroprenolol).
Main Results:
- Fenoterol induced significant desensitization of beta-receptors in the fetal lung.
- No significant desensitization of beta-receptors was observed in the pregnant doe's lung.
- The affinity of beta-adrenergic receptors remained largely unchanged.
Conclusions:
- Fenoterol can induce beta-receptor desensitization specifically in the fetal lung.
- Long-term use of beta-2 sympathomimetics may lead to diminished fetal lung function due to adrenoreceptor desensitization.
- These findings highlight potential risks of antenatal beta-agonist therapy.