The effects of dopamine, serotonin and influences associated with meconium on lung liquid production in in vitro lungs from fetal guinea pigs (cavia porcellus)
Creators: name: Chua, Beverly A.
Publisher: name: University of British Columbia
Year: 2009

description: Lungs from near term fetal guinea pigs (58-67 days of gestation) were supported in vitro for three hours; lung liquid production was monitored by a dye dilution technique. 42 preparations (61 + 1 days of gestation, 81.9 ± 9.5 g (SD) body weight) were used to study the effects of dopamine placed in the outer saline for the middle hour. At concentrations of 10⁻⁷ and 10⁻⁶ M , dopamine produced significant reductions of fluid production; at 10⁻⁵ M, there was complete arrest of production. Dopamine, at 10⁻⁴ M , produced fluid reabsorption. The linear log concentration response curve (r=0.99) showed a theoretical threshold at 1.7 x 10⁻⁹ M dopamine. Responses from dopamine involved dopaminergic receptors, since they were abolished by haloperidol (10⁻⁵ M) (n=24), a non-specific dopamine antagonist. Activation was through D₂ receptors, since responses were abolished by 10⁻⁵ M domperidone (D₂-receptor antagonist) (n=24), but unaffected by 10⁻⁵ M SCH 23390 (D₁-receptor antagonist) (n=24). Reductions by dopamine were resistant to amiloride (IO⁻⁶, 10⁻⁵ and IO⁻⁴ M) (n=66) and benzamil (10⁻⁵ M) (n=24). 36 preparations (61 ± 1 days of gestation, 77.7 + 11.5 g (SD) body weight) treated with serotonin showed about 50% reduction in fluid (10⁻⁷, 10⁻⁶ and 10⁻⁵ M). Below 10⁻⁷ M serotonin, there was a linear log concentration response curve (r=0.98), and the line of best fit suggested a theoretical threshold of 5 x IO⁻⁹ M . Preparations from 10 more mature fetuses, (65 ± 1 days of gestation, 126.2 + 13.2 g (SD) body weight) showed significantly greater responses. Maximal responses at 10⁻⁷ M involved serotonergic receptors since they were eliminated by the general serotonin antagonist, cyproheptadine (10⁻⁶ M) (n=24). In addition, 10⁻⁶ M amiloride abolished effects by serotonin (n=24). 6 untreated lungs from meconium-stained fetuses produced lung fluid consistently throughout 3 hours of incubation. However, rates of lactate production throughout experimentation were higher than rates produced by untreated, meconium-free fetuses. This suggested that these meconium-influenced lungs have increased their glycolytic metabolism to support normal fluid production. Twelve meconium-free preparations treated with 10⁻³ M 2,4-dinitrophenol (DNP) showed strong reabsorptions, and total loss of lactate increased by 3.8-fold during treatment. These reabsorptions resembled those produced after 2 x 10⁻⁴ M DNP; however, total lactate loss during treatment with 2 x 10⁻⁴ M DNP only doubled. This suggested that reabsorptions can operate on mainly glycolytic processes. In contrast, twelve lungs taken from meconium-stained fetuses and treated with 2 x 10⁻⁴ M DNP showed no change in fluid production; however, lactate production again doubled. It appeared that these lungs, although already showing above average glycolytic activity, were still capable of increasing it. Failure to reabsorb fluid may be due to a disruption in the link between metabolic processes and the reabsorptive mechanism. These studies suggest that lungs from meconium-stained fetuses have differences concerning fluid production and reabsorption processes. Furthermore, in the guinea pig, dopamine may play a role in reducing lung fluid production or initiating reabsorption close to birth, but by processes other than Na+ transport. Serotonin can slow lung liquid production or cause reabsorption; the effect increases close to term and is due to activation of amiloride-sensitive Na+ channels.