TY - JOUR
T1 - Atrial natriuretic peptide modulates alveolar type 2 cell adenylyl and guanylyl cyclases and inhibits surfactant secretion
AU - Panchenko, Mikhail P.
AU - Joyce-Brady, Martin
AU - Starikova, Marina G.
AU - Oakes, Sean M.
AU - Adachi, Roberto
AU - Brody, Jerome S.
AU - Dickey, Burton F.
N1 - Funding Information:
We thank Lukas Kolm for technical assistance, Dr. Roy Levine for help with the Northern blots, and Dr. Jack Thornby for assistance with the statistical analyses. This work was supported by grants from the National Institutes of Health (HL 34768, HL 47049, and HL 43161).
PY - 1998/5/27
Y1 - 1998/5/27
N2 - Alveolar epithelial type 2 (T2) cells isolated from the lungs of adult rats responded to exogenous atrial natriuretic peptide (ANP) by two signalling mechanisms. First, ANP induced a dose-dependent reduction of ligand-stimulated adenylyl cyclase activity and cAMP accumulation. This effect was inhibited by the addition of GDPβS or by pretreatment with pertussis toxin (PT), consistent with mediation by a Gi protein(s). PT- catalyzed [32P]ADP-ribosylation, immunoblots with specific antisera, and Northern blot analysis demonstrated that T2 cells contain the G-proteins Gi2 and Gi3 which could transduce this signal. ANP also promoted PT- insensitive, dose-dependent accumulation of cGMP, consistent with activation of a receptor guanylyl cyclase. Isoproterenol-stimulated phosphatidylcholine secretion was markedly attenuated by ANP, and this effect was inhibited by PT pretreatment, consistent with mediation by a Gi protein(s). These data indicate that in addition to the lung being a major clearance organ for circulating ANP, lung parenchymal cells are targets of ANP action.
AB - Alveolar epithelial type 2 (T2) cells isolated from the lungs of adult rats responded to exogenous atrial natriuretic peptide (ANP) by two signalling mechanisms. First, ANP induced a dose-dependent reduction of ligand-stimulated adenylyl cyclase activity and cAMP accumulation. This effect was inhibited by the addition of GDPβS or by pretreatment with pertussis toxin (PT), consistent with mediation by a Gi protein(s). PT- catalyzed [32P]ADP-ribosylation, immunoblots with specific antisera, and Northern blot analysis demonstrated that T2 cells contain the G-proteins Gi2 and Gi3 which could transduce this signal. ANP also promoted PT- insensitive, dose-dependent accumulation of cGMP, consistent with activation of a receptor guanylyl cyclase. Isoproterenol-stimulated phosphatidylcholine secretion was markedly attenuated by ANP, and this effect was inhibited by PT pretreatment, consistent with mediation by a Gi protein(s). These data indicate that in addition to the lung being a major clearance organ for circulating ANP, lung parenchymal cells are targets of ANP action.
KW - Adenylyl cyclase
KW - Atrial natriuretic peptide
KW - Guanylyl cyclase
KW - Lung epithelial type 2 cell
KW - Secretion
KW - Surfactant
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U2 - 10.1016/S0167-4889(98)00023-8
DO - 10.1016/S0167-4889(98)00023-8
M3 - Article
C2 - 9622608
AN - SCOPUS:0032572106
SN - 0167-4889
VL - 1403
SP - 115
EP - 125
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 1
ER -