Activation of G proteins may inhibit or stimulate surfactant secretion in rat alveolar type II cells.
To investigate how G proteins regulate surfactant secretion, we subjected rat alveolar type II cells to conditions known to activate or to inactivate G proteins. AlF-4, which activates G proteins, inhibited secretion in intact cells. Guanosine-5'-O-(3-thiotriphosphate), which activates G proteins in permeabilized cells, stimulated secretion at basal cytosolic [Ca2+], but inhibited secretion at higher [Ca2+]. In contrast, guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), which inactivates G proteins, stimulated secretion at each [Ca2+] tested. Because treatment with GDP beta S stimulated secretion at basal cytosolic [Ca2+], surfactant secretion appears to be subject to G protein-regulated tonic inhibition. Pertussis toxin (PTX) inhibited terbutaline- and ionomycin-stimulated secretion in intact cells, but did not inhibit secretion stimulated by either forskolin or 8-bromoadenosine 3',5'-cyclic monophosphate. Inhibition by PTX of terbutaline-stimulated, but not 8-bromoadenosine 3',5'-cyclic monophosphate- or forskolin-stimulated secretion, suggests that PTX-sensitive G proteins regulate beta-adrenergic-stimulated surfactant secretion proximal to second messenger generation. Inhibition of ionomycin-stimulated secretion, however, suggests that PTX-sensitive G proteins may also regulate non-receptor-mediated secretory events.
Pian
M S
MS
Cardiovascular Research Institute, University of California, San Francisco, California 94143-0130.
Dobbs
L G
LG
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D008297:Male; D010539:Permeability; D037342:Pertussis Toxin; D010713:Phosphatidylcholines / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012969:Sodium Fluoride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D006150:Guanine Nucleotides; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D010566:Virulence Factors, Bordetella; D000077410:Aluminum Chloride; D012969:Sodium Fluoride; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins