The effect of dopamine on lung liquid production by in vitro lungs from fetal guinea-pigs

1. The neuroendocrine system of the lungs has no clear function. However, previous studies of one of its products, somatostatin, have implicated it in lung liquid removal at birth. The present study extends this concept by investigating the effects of dopamine, a major product of this system, on lung liquid reabsorption. 2. The effects of dopamine on fetal lung liquid production and reabsorption were tested on in vitro lungs from fetal guinea-pigs of 60 +/- 2 days of gestation (term = 67 days). Dopamine was placed in the outer bathing saline during the middle hour of 3 h incubations. Fluid movements across the pulmonary epithelium were monitored by a dye dilution method, and changes in rates over 1 h intervals were tested for significance by analysis of variance and regression analysis. 3. Dopamine was able to reduce fluid production or cause reabsorption (based on 42 preparations). Control preparations and those given 10-8 M dopamine showed no significant changes; those given higher concentrations showed significant reductions in production or reabsorption (P < 0.025 to P < 0.0005), according to dose (42.6 +/- 10.8% reduction at 10-7 M; 75.4 +/- 5.9% reduction at 10-6 M; 92.1 +/- 7.0% reduction at 10-5 M and 121.4 +/- 12.8% (reabsorption) at 10-4 M dopamine). The linear log dose-response curve (r = 0.99) showed a theoretical threshold at 1.7 x 10-9 M dopamine. 4. Effects were mediated through specific dopamine receptors (based on 78 preparations). Dopamine at 10-6 M was tested together with each of three dopamine receptor antagonists at 10-5 M. The general dopamine receptor antagonist haloperidol and the more specific D2 receptor blocker domperidone both abolished responses, but the D1 receptor antagonist SCH 23390 was without effect. This suggested that D2 dopamine receptors mediated the responses, and that responses were not due to conversion of dopamine to adrenaline or noradrenaline. 5. There was no evidence that responses involved amiloride-sensitive Na+ transport (based on 54 preparations). Apical amiloride at 10-6, 10-5 or 10-4 M, and the more specific Na+ channel blocker benzamil (10-5 M), had no effect on responses to dopamine, in contrast to their effects on responses to adrenaline in sheep. 6. It is suggested that internal release of dopamine by the neuroendocrine system of the lungs may influence lung liquid reabsorption at birth. This system, which also produces somatostatin, another agent active on lung liquid production, is maximally developed and activated at birth; it is also deficient in hyaline membrane disease.