Effects of PKA inhibitors, H-compounds, on epithelial Na+ channels via PKA-independent mechanisms

Life Sci. 1999;65(10):PL109-14. doi: 10.1016/s0024-3205(99)00341-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / chemistry
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Amiloride / pharmacology
  • Animals
  • Carbazoles*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Indoles / chemistry
  • Indoles / pharmacology
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology
  • Myristic Acid / pharmacology
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Sodium Channels / drug effects*
  • Structure-Activity Relationship
  • Sulfonamides*
  • Terbutaline / pharmacology

Substances

  • Carbazoles
  • Enzyme Inhibitors
  • Indoles
  • Isoquinolines
  • Pyrroles
  • Sodium Channels
  • Sulfonamides
  • Myristic Acid
  • H 85
  • KT 5720
  • Amiloride
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide
  • Sodium
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Terbutaline