Purinergic and nitrergic junction potential in the human colon

Area of Science:

• Gastroenterology
• Neuroscience
• Pharmacology

Background:

• The human colon utilizes neurotransmitters for regulating muscle function.
• Nitric oxide (NO) and adenosine triphosphate (ATP) are implicated as potential mediators of colonic relaxation.
• Understanding their distinct roles is crucial for comprehending colonic motility disorders.

Purpose of the Study:

• To investigate the junctional transmission of NO and ATP in the human colon.
• To characterize the electrophysiological and mechanical responses mediated by NO and ATP.
• To elucidate the complementary functions of these neurotransmitters in colonic relaxation.

Main Methods:

• Human colonic circular muscle strips were utilized.
• Muscle bath techniques were employed to assess mechanical responses.
• Microelectrode techniques were used to record electrophysiological events, including inhibitory junction potentials (IJPs).
• Pharmacological agents, including NO donors, synthase inhibitors, and purinergic antagonists, were applied.

Main Results:

• Nitric oxide (NO) donors induced sustained relaxation, whereas P2Y receptor agonists did not.
• Inhibition of NO synthase increased spontaneous motility, while P2Y antagonists did not.
• Electrical field stimulation (EFS) at low frequencies evoked fast IJPs (fIJPs) sensitive to P2Y antagonists, indicating ATP release.
• EFS at higher frequencies elicited biphasic IJPs, with initial MRS 2179-sensitive and subsequent L-NNA-sensitive hyperpolarization, demonstrating both ATP and NO involvement.
• Both NO and ATP were required to fully block EFS-induced relaxation at higher frequencies.
• Single pulses induced rundown of fIJPs, independent of hyperpolarization degree or specific inhibitors, suggesting a complex release or signaling mechanism for ATP.

Conclusions:

• Single electrical pulses trigger adenosine triphosphate (ATP) release from enteric motor neurons, causing fast inhibitory junction potentials (fIJPs) and transient relaxation.
• Nitric oxide (NO) is released at higher stimulation frequencies, mediating sustained hyperpolarization and relaxation.
• These distinct mechanisms, phasic (ATP) and tonic (NO), likely serve complementary roles in regulating human colonic smooth muscle function.