Effects of PKA inhibitors, H-compounds, on epithelial Na+ channels via PKA-independent mechanisms.
The Na+ transport in alveolar type II epithelial cells of rat fetal lung was stimulated by cAMP, which is generally thought to act through activation of protein kinase A (PKA). PKA inhibitors (H8, H89 and H7) stimulated amiloride-sensitive Na+ transport in the alveolar type II epithelial cells. H85, an inactive form of H89 as a PKA inhibitor, had also mimicked the stimulatory action of H89 on the Na+ transport. On the other hand, another type of PKA inhibitor, KT5720 or myristoylated PKA inhibitory peptide [14-22] amide, did not stimulate the Na+ transport, but inhibited the Na+ transport unlike H-compounds. These observations suggest that H-compounds act on the Na+ transport depending on the structure.
Niisato
N
N
The Hospital for Sick Children Research Institute, Department of Pediatrics and Institute of Medical Science, The University of Toronto Faculty of Medicine, Ontario, Canada.
Ito
Y
Y
Marunaka
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000737:chemistry / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D019814:Myristic Acid / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D013726:Terbutaline / Q000494:pharmacology
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D011758:Pyrroles; D015222:Sodium Channels; D013449:Sulfonamides; D019814:Myristic Acid; C071449:H 85; C057416:KT 5720; D000584:Amiloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D012964:Sodium; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013726:Terbutaline