Regulation of lung surfactant secretion by the A sub 2 adenosine receptor

Conference · Fri May 01 04:00:00 EDT 1987 · Federation Proceedings, Federation of American Societies for Experimental Biology; (USA)

OSTI ID:5084574

Gilfillan, A M; Gobran, L I; Rooney, S A ^[1]

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1. Yale Univ. School of Medicine, New Haven, CT (USA)

The authors previously reported that adenosine (A) stimulates secretion of phosphatidylcholine (PC), the major component of surfactant, in type II pneumocytes. To determine how this effect is mediated we examined the effect of P{sub 1} purinoceptor agonists -N{sup 6}-phenylisoprpyl-A (PIA), 5{prime}-N-ethylcarboxyamido-A (NECA), 2-chloro-A (CA) - and antagonists - theophylline (T) and 8-phenyltheophylline (8PT) - on PC secretion and cAMP levels in type II cells isolated from the adult rat. The cells were preincubated with {sup 3}H-choline for 20 h, transferred to fresh medium and incubated {plus minus} test agents for 1.5 h after which {sup 3}H-PC in the cells and medium was measured. A and its analogs stimulated PC secretion in a dose-dependent manner. At the optimal concentration (A, 1 mM; analogs, 0.01 mM) secretion was stimulated approx. 2-fold from a basal rate of 0.08-1.02% of total PC in the medium after 1.5 h. The potency order was NECA>CA=L-PIA>A>D-PIA. The EC{sub 50} for NECA was 8.9 {times} 10{sup {minus}8}M. The effect of NECA was significantly inhibited by 8PT (0.01 mM) and T (0.05 mM). NECA, A and L-PIA increased cellular cAMP levels 34, 12 and 8 fold, respectively, from a basal level of 0.23-0.28 pmol/10{sup 6} cells. These data suggest that the A{sub 2} subtype of the P{sub 1} receptor mediates the effect of A. In newborn rabbits, lung lavage PC increased form 24.1 {plus minus} 1.6 ug P/g lung dry wt at 0 h to 62.6 {plus minus} 7.7 after breathing for 3 h (n=13). 8PT (15 mg/kg, i.m.) at 0 h decreased the PC content at 3 h by 29% to 44.4 {plus minus} 5.1 ug/g. This suggests a functional role for the P{sub 1} receptor in lung surfactant secretion.

• OSTI ID: 5084574
• Report Number(s): CONF-870644--
• Conference Information: Journal Name: Federation Proceedings, Federation of American Societies for Experimental Biology; (USA) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
AMP
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
CHEMICAL ACTIVATION
CHOLINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ESTERS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LECITHINS
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
NEONATES
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
PROTEINS
QUATERNARY COMPOUNDS
RABBITS
RATS
REACTION KINETICS
RECEPTORS
RESPIRATORY TRACT CELLS
RESPONSE MODIFYING FACTORS
RIBOSIDES
RODENTS
SECRETION
SURFACTANTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES