Enteric glia exhibit P2U receptors that increase cytosolic calcium by a phospholipase C-dependent mechanism

J Neurochem. 1996 Feb;66(2):604-12. doi: 10.1046/j.1471-4159.1996.66020604.x.


Calcium signaling in fura-2 acetoxymethyl ester-loaded enteric glia was investigated in response to neuroligands; responses to ATP were studied in detail. Carbachol (1 mM), glutamate (100 microM), norepinephrine (10 microM), and substance P (1 microM) did not increase the intracellular calcium concentration ([Ca2+]i) in cultured enteric glia. An increasing percentage of glia responded to serotonin (4%; 100 microM), bradykinin (11%; 10 microM), and histamine (31%; 100 microM), whereas 100% of glia responded to ATP (100 microM). ATP-evoked calcium signaling was concentration dependent in terms of the percentage of glia responding and the peak [Ca2+]i achieved; responses were pertussis toxin insensitive. Based on responsiveness of enteric glia to purinergic agonists and peak [Ca2+]i evoked, ATP = UTP > ADP > beta, gamma-methyleneadenosine 5'-triphosphate >> 2-methylthioadenosine 5'-triphosphate = alpha,beta-methyleneadenosine 5'-triphosphate = AMP = adenosine, suggesting a glial P2U receptor. Depletion of D-myo-inositol 1,4,5-trisphosphate-sensitive calcium stores by thapsigargin (10 microM) abolished glial responses to ATP. Similarly, calcium responses were decreased 92% by U-73122 (10 microM), an inhibitor of phospholipase C, and 93% by the phorbol ester phorbol 12-myristate 13-acetate (100 nM), an activator of protein kinase C. Thus, cultured enteric glia can respond to neurotransmitters with increases in [Ca2+]i. Our data suggest that glial responses to ATP are mediated by a P2U receptor coupled to activation of phospholipase C and release of intracellular calcium stores.

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Culture Techniques
  • Cytosol / metabolism*
  • Extracellular Space / metabolism
  • Guinea Pigs
  • Immunohistochemistry
  • Male
  • Myenteric Plexus / metabolism*
  • Neuroglia / metabolism*
  • Osmolar Concentration
  • Pertussis Toxin
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2Y2
  • Terpenes / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thapsigargin
  • Type C Phospholipases / physiology*
  • Virulence Factors, Bordetella / pharmacology


  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y2
  • Terpenes
  • Virulence Factors, Bordetella
  • Thapsigargin
  • Adenosine Triphosphate
  • Pertussis Toxin
  • Type C Phospholipases
  • Calcium-Transporting ATPases
  • Tetradecanoylphorbol Acetate
  • Calcium