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Neurotransmitters involved in the fast inhibitory junction potentials in mouse distal colon

Rosa Serio1, Massimiliano Alessandro, Maria Grazia Zizzo

  • 1Dipartimento di Biologia cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. rserio@unipa.it

European Journal of Pharmacology
|February 1, 2003
PubMed

Insights

Adenosine 5'-triphosphate (ATP) acts as a key inhibitory neurotransmitter in the murine colon, mediating the fast component of nerve-evoked inhibitory junction potentials (fast IJP) via P2Y receptors. Pituitary adenylate cyclase activating peptide (PACAP) appears to modulate this inhibitory pathway.

Area of Science:

  • Gastrointestinal physiology
  • Neuropharmacology
  • Smooth muscle biology

Background:

  • The nonadrenergic, noncholinergic (NANC) inhibitory neurotransmission in the gut is complex.
  • Adenosine 5 -triphosphate (ATP) and pituitary adenylate cyclase activating peptide (PACAP) are implicated as potential inhibitory mediators.

Purpose of the Study:

  • To elucidate the roles of ATP and PACAP in mediating the fast inhibitory junction potential (fast IJP) in murine colon circular muscle.
  • To identify the specific receptors and pathways involved in this inhibitory neurotransmission.

Main Methods:

  • Electrophysiological recordings of nerve-evoked inhibitory junction potentials (IJP) in murine colon.
  • Pharmacological characterization using receptor antagonists (apamin, suramin, PACAP-(6-38)) and agonists (ADPbetaS, alpha,beta-meATP).
  • Assessment of neurotransmitter effects on membrane potential and their resistance/sensitivity to various inhibitors (tetrodotoxin, L-NAME).

Main Results:

  • Fast IJP was antagonized by apamin and suramin, and abolished by P2Y receptor desensitization with ADPbetaS.
  • ATP induced tetrodotoxin-resistant hyperpolarization, antagonized by apamin, suramin, and P2Y/P2X receptor desensitization.
  • PACAP-(1-27) induced hyperpolarization sensitive to PACAP-(6-38), apamin, and P2Y receptor desensitization, but reduced by tetrodotoxin.

Conclusions:

  • An endogenous P2Y purinoceptor ligand, likely ATP-like, is the primary mediator of the fast IJP in murine colon circular muscle.
  • PACAP may play a neuromodulatory role within this inhibitory pathway, influencing neurotransmitter release or receptor sensitivity.

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