Inhibition of epithelial Na sup + transport by atriopeptin, protein kinase c, and pertussis toxin
- Massachusetts General Hospital, Boston (USA)
The authors have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na{sup +} by atrial natriuretic peptide and 8-bromoguanosine 3{prime},5{prime}-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK{sub i}. Using {sup 22}Na{sup +} fluxes, they further investigated the modulation of Na{sup +} transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na{sup +} uptake in a time- and concentration-dependent manner. Oleoyl 2-acetylglycerol and phorbol 12-myristate 13-acetate, activators of protein kinase c, inhibit Na{sup +} uptake by 93 {plus minus} 13 and 51 {plus minus} 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK{sub i} cells, inhibits {sup 22}Na{sup +} influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na{sup +} uptake. These events may be sequentially involved in the action of atrial natriuretic peptide.
- OSTI ID:
- 5036431
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 253:2; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL ISOTOPES
AMINES
ANIMAL TISSUES
ANTIGENS
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
CARCINOGENS
CELL CULTURES
CHEMISTRY
ENZYMES
EPITHELIUM
ESTERS
GUANINE
GUANOSINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INHIBITION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LIGHT NUCLEI
MATERIALS
MEMBRANE TRANSPORT
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
PURINES
RADIOISOTOPES
RIBOSIDES
SODIUM 22
SODIUM ISOTOPES
TISSUES
TOXIC MATERIALS
TOXINS
TRANSFERASES
YEARS LIVING RADIOISOTOPES