Ca2+-independent protein kinase C isoforms may modulate parietal cell HCl secretion

Area of Science:

• Cell Biology
• Gastroenterology
• Biochemistry

Background:

• Parietal cell HCl secretion is regulated by cAMP and Ca2+ pathways.
• The role of protein kinase C (PKC) in regulating gastric acid secretion remains controversial.

Purpose of the Study:

• To investigate the involvement of PKC isoforms in regulating rabbit parietal cell HCl secretion.
• To identify specific PKC isoforms and their potential targets in parietal cells.

Main Methods:

• Gastric glands from rabbits were used to measure acid secretion (aminopyrine accumulation).
• PKC inhibitors (calphostin C, chelerythrine chloride, staurosporine, Ro 31-8220, Gö 6976, bisindolylmaleimide I hydrochloride) were employed.
• Western blot analysis identified PKC isozyme profiles in enriched parietal cells.
• Immunolocalization and protein phosphorylation studies were conducted.

Main Results:

• Parietal cells express novel (PKC-epsilon, PKC-mu) and atypical (PKC-iota, PKC-lambda, PKC-zeta) PKC isoforms, with low classical isoform expression.
• High concentrations of Ro 31-8220 potentiated histamine- and carbachol-stimulated acid secretion.
• Ro 31-8220 inhibited phosphorylation of pp66 and ezrin, a cytoskeletal protein.
• PKC-epsilon was localized to the actin-rich compartment, and pp66 was found in an insoluble fraction.

Conclusions:

• Novel PKC isoforms may negatively regulate gastric HCl secretion.
• PKC-dependent phosphorylation of ezrin and potentially pp66 might be involved in regulating parietal cell morphological changes during secretion.