Vasopressin signal transduction in rat type II pneumocytes.
Previous studies demonstrate that in cultured type II pneumocytes, [Arg8]-vasopressin (AVP) stimulates surfactant secretion independent of adenosine 3',5'-cyclic monophosphate (cAMP). In the current study AVP stimulated a 50% loss of radioactive phosphatidylinositol 4,5-bisphosphate (PIP2) within 15 s. Consistent with AVP-induced PIP2 hydrolysis was an increased appearance of the two breakdown products 1,2-diacylglycerol (1,2-DAG) and inositol 1,4,5-trisphosphate (IP3). Also, AVP stimulated the appearance of radiolabel in phosphatidic acid (PA) suggesting that the conversion of 1,2-DAG to PA could be used for PIP2 resynthesis. The effects of AVP on PIP2 and IP3 were mimicked by the bioactive AVP fragment and inhibited by the specific AVP1 antagonist. The EC50 for AVP on IP3 production was 6 nM. AVP stimulated protein kinase C (PK-C) activity twofold over the basal activity of 0.74 +/- 0.07 nmol P.min-1.mg protein-1 but did not activate cAMP-dependent protein kinase activity. The AVP1 antagonist inhibited AVP activation of PK-C. Therefore, activation of the AVP1 receptor resulted in PIP2 hydrolysis for signal transduction, PK-C activation, and surfactant secretion.
Brown
L A
LA
Department of Pediatrics, Emory University, Atlanta, Georgia.
Chen
M
M
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014667:Vasopressins
D004075:Diglycerides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D014667:Vasopressins; D001127:Arginine Vasopressin; D011494:Protein Kinases; D011493:Protein Kinase C