Guanosine negatively modulates the gastric motor function in mouse

Area of Science:

• Gastroenterology
• Pharmacology
• Molecular Biology

Background:

• Gastric motor function is crucial for digestion and nutrient absorption.
• The role of purine nucleosides, such as guanosine, in regulating gastric motility is not fully understood.
• Investigating guanosine's effects can reveal novel mechanisms influencing gastrointestinal physiology.

Purpose of the Study:

• To investigate the effects of guanosine on gastric motor function in mice.
• To determine the in vivo gastric emptying rate and in vitro gastric mechanical activity influenced by guanosine.
• To elucidate the cellular and molecular pathways mediating guanosine's actions on the stomach.

Main Methods:

• In vivo gastric emptying studies using gastric gavage of guanosine.
• In vitro analysis of spontaneous gastric mechanical activity and intraluminal pressure changes.
• Pharmacological inhibition of enzymes (purine nucleoside phosphorylase, soluble guanylyl cyclase, adenylyl cyclase), transporters, receptors, and ion channels.
• Measurement of cyclic adenosine monophosphate (cAMP) levels using ELISA.

Main Results:

• Guanosine administration delayed gastric emptying in a dose-dependent manner.
• Guanosine induced concentration-dependent relaxation of isolated stomach preparations.
• The relaxation was mediated by cellular uptake and adenylyl cyclase activation, leading to increased intracellular cAMP levels.
• Guanosine's effects were independent of neural pathways, adenosine receptors, and potassium channel activation.

Conclusions:

• Guanosine negatively modulates mouse gastric motor function by reducing gastric emptying and inducing muscular relaxation.
• The observed relaxation is dependent on cellular uptake and involves the cAMP signaling pathway.
• These findings highlight a novel role for guanosine in regulating gastric motility, independent of established neural and ionic mechanisms.