Do purinergic receptors play a role in the regulation of lung surfactant production
Pulmonary surfactant, of which phosphatidylcholine (PC) is a major component, is produced by the type II pneumocyte. PC secretion in type II cells is stimulated by beta-agonists, leukotrienes and agents that activate protein kinase C. Since the influence of purinergic agonists on surfactant secretion has not been reported previously they examined the effects of adenosine and its phosphorylated derivatives on PC secretion in type II cells. The cells were isolated from adult rats and cultured for 20 h in medium containing serum, antibiotics and /sup 3/H-choline. They were then transferred to fresh serum-free medium and incubated with the test agents for 90 min after which /sup 3/H-PC in the cells and medium was measured. Adenosine, AMP, ADP and ATP all stimulated PC secretion. The effects were dose-dependent in the range 10/sup -8/ to 10/sup -3/ M. At 10/sup -3/M, adenosine stimulated secretion by 140% from a basal rate of 0.91 +/- 0.06 (/sup 3/H-PC in the medium as % of that in cells + medium) to 2.19 +/- 0.26 (n = 6, P < 0.005, paired t test), AMP stimulated by 140% from 0.87 +/- 0.07 to 2.09 +/- 0.09 (n = 4, P < 0.002), ADP by 570% from 0.84 +/- 0.05 to 5.65 +/- 0.34 (n = 4, P < 0.002) and ATP by 410% from 0.84 +/- 0.04 to 4.32 +/- 0.35 (n = 5, P < 0.001). The EC/sub 50/ values for adenosine, AMP, ADP and TP were 3.0, 0.6, 20.0 and 5.0 x 10/sup -6/ M, respectively. None of the agents increased release of lactate dehydrogenase or PC synthesis as determined by choline incorporation. The effects are therefore likely to be directly on secretion rather than secondary to PC synthesis or cell injury.
- Research Organization:
- Yale Univ. School of Medicine, New Haven, CT
- OSTI ID:
- 5332899
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
Similar Records
ATP and adenosine stimulate phosphatidylcholine secretion in type II pneumocytes by different mechanisms
Effects of thiazinamium chloride on surfactant production in primary cultures of type II cells isolated from adult rat lung
Related Subjects
ADENOSINE
BIOLOGICAL EFFECTS
ADP
AMP
ATP
PHOSPHOLIPIDS
SECRETION
SURFACTANTS
CELL CULTURES
CHOLINE
DOSE-RESPONSE RELATIONSHIPS
LUNGS
RATS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BODY
DRUGS
ESTERS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PROTEINS
QUATERNARY COMPOUNDS
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques