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Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Rat gastric mucosal adenylyl cyclase
Gastroenterology
|February 1, 1977
Summary
Gastric acid secretion inhibitors like Prostaglandin E1 stimulated rat stomach mucosal adenylyl cyclase. However, common gastric acid secretagogues did not activate this enzyme, suggesting cyclic AMP does not mediate their actions in rats.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Signaling
Background:
- Prostaglandin E1, epinephrine, secretin, and glucagon are known inhibitors of gastric acid secretion.
- The role of cyclic AMP (cAMP) in mediating gastric acid secretion is not fully understood.
Purpose of the Study:
- To investigate the effect of various agents on adenylyl cyclase activity in rat gastric mucosa.
- To determine if cAMP mediates the action of gastric acid secretagogues in rats.
Main Methods:
- Adenylyl cyclase activity was measured in membrane fractions of rat stomach corpus mucosa.
- Enzyme activity was assessed in response to Prostaglandin E1, epinephrine, secretin, glucagon, 5'-guanylyl-imidodiphosphate, sodium fluoride, pentagastrin, histamine, and carbachol.
- Kinetic analysis was performed to determine the enzyme's affinity for ATP.
Main Results:
- Prostaglandin E1, epinephrine, secretin, and glucagon stimulated adenylyl cyclase activity.
- 5'-guanylyl-imidodiphosphate and sodium fluoride also activated the enzyme.
- Pentagastrin, histamine, and carbachol did not affect basal or Prostaglandin E1-stimulated adenylyl cyclase activity in rat gastric mucosa.
- Histamine stimulated adenylyl cyclase in guinea pig gastric fundic mucosa, but not in rat mucosa.
- The enzyme exhibited Michaelis-Menten kinetics with an apparent Km of 0.25 mM for ATP.
Conclusions:
- The findings do not support the hypothesis that cAMP mediates the actions of gastric acid secretagogues on parietal cells in the rat.
- Adenylyl cyclase in rat gastric mucosa is stimulated by inhibitors of gastric acid secretion but not by secretagogues.
- Differences in enzyme response between rat and guinea pig gastric mucosa suggest species-specific mechanisms.
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