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Cytochalasin inhibition of isolated rat gastric parietal cell function
Abstract:
Submicrogram concentrations (0.04-0.29 microM) of the microfilament disrupting agents cytochalasins D, E, and B (CD, CE, CB) were shown to inhibit secretagogue-stimulated 14C-aminopyrine accumulation (AP) in isolated rat gastric mucosal parietal cells. The microtubule disrupting agent colchicine had little influence on AP accumulation. Histamine- and dibutyryl cyclic AMP (DbcAMP)-stimulated AP accumulation was inhibited with an order of potency CD greater than CE approximately equal to CB. CB inhibition of these secretagogue actions was, however, only approximately 65-70% of the maximal stimulated response, whereas CD and CE caused 100% inhibition. On the other hand, carbamylcholine-stimulated AP accumulation was inhibited 100% by all cytochalasins tested with an order of potency CD approximately equal to CE greater than CB. These data are discussed in relation to acid secretagogue-induced morphological changes involving actin filament organization in parietal cells.
Insights
Cytochalasins D, E, and B inhibit acid secretion in rat gastric parietal cells by disrupting microfilaments. These findings link actin organization to acid production stimulated by secretagogues.
Area of Science:
- Cell Biology
- Gastroenterology
- Pharmacology
Background:
- Parietal cells in the gastric mucosa are responsible for acid secretion.
- Secretagogues stimulate acid production through complex cellular pathways.
- The role of the actin cytoskeleton in regulating parietal cell function is not fully understood.
Purpose of the Study:
- To investigate the effect of microfilament and microtubule disrupting agents on acid secretion in isolated rat gastric parietal cells.
- To determine the role of actin filament organization in mediating secretagogue-stimulated acid production.
Main Methods:
- Isolated rat gastric mucosal parietal cells were used.
- 14C-aminopyrine accumulation (AP) was measured as an indicator of acid secretion.
- Cells were treated with cytochalasins D, E, and B (microfilament disruptors) and colchicine (microtubule disruptor).
- Stimulation of AP accumulation was induced by histamine, dibutyryl cyclic AMP (DbcAMP), and carbamylcholine.
Main Results:
- Submicrogram concentrations of cytochalasins D, E, and B significantly inhibited secretagogue-stimulated AP accumulation.
- Colchicine had minimal effect on AP accumulation.
- The order of potency for inhibition of histamine- and DbcAMP-stimulated AP accumulation was CD > CE ≈ CB.
- Cytochalasins D and E caused 100% inhibition, while cytochalasin B caused 65-70% inhibition.
- All cytochalasins tested inhibited carbamylcholine-stimulated AP accumulation by 100%.
Conclusions:
- Microfilament integrity is crucial for mediating acid secretion stimulated by various secretagogues in rat gastric parietal cells.
- Cytochalasins D, E, and B interfere with actin filament organization, thereby inhibiting acid production.
- These findings suggest a direct link between actin cytoskeleton dynamics and the regulation of gastric acid secretion.