Effects of acetylcholine on lung liquid production by in vitro lungs from fetal guinea pigs.
Lungs from near-term fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Untreated preparations produced lung liquid with no significant changes (ANOVA; regression analysis) (rates in successive hours, initial study: 1.37 +/- 0.30, 1.36 +/- 0.30, and 1.28 +/- 0.27 mL.kg-1 body weight.h-1; n = 6). Preparations given acetylcholine at 10(-4) (n = 6), 10(-5) (n = 6), and 10(-6) M (n = 18) during the middle hour showed marked and significant fluid reabsorption (p < 0.025-0.0005); 10(-8) M acetylcholine was without effect. Reductions were linearly related to log concentration of acetylcholine (r = 0.97; theoretical threshold, 1.0 x 10(-7) M acetylcholine). Atropine, at 10(-5) M, greatly reduced responses to acetylcholine, and all reabsorptions were abolished; 10(-4) M atropine completely abolished all responses to acetylcholine; atropine alone had no effect (based on 48 studies). The alpha-adrenoreceptor antagonist phentolamine (1.78 x 10(-5) M) abolished the effects of 10(-6) M acetylcholine, but had no effect alone (based on 48 studies); the beta-adrenoreceptor antagonist propranolol (10(-5) M) had no effect on responses to 10(-6) M acetylcholine (based on 24 studies). It is suggested that acetylcholine at physiological levels can produce lung liquid reabsorption by activating muscarinic receptors and releasing catecholamines within the lungs; these catecholamines act via alpha-receptors. This raises the possibility of neural controls of lung liquid reabsorption during the early stages of delivery or neonatal life.
Woods
B A
BA
Department of Obstetrics, and Gynecology, University of British Columbia, Vancouver, Canada.
Ng
W
W
Thakorlal
D
D
Liu
A L
AL
Perks
A M
AM
D000042:Absorption; D000109:Acetylcholine / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D010646:Phentolamine