Endothelin-mediated calcium response and inositol 1,4,5-trisphosphate release in neuroblastoma-glioma hybrid cells (NG108-15): cross talk with ATP and bradykinin

J Neurochem. 1993 Feb;60(2):454-60. doi: 10.1111/j.1471-4159.1993.tb03172.x.

Abstract

Addition of endothelins (ETs) to neuroblastoma-glioma hybrid cells (NG108-15) induced increases in cytosolic free Ca2+ ([Ca2+]i) levels of labeled inositol monophosphates and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. The increases in [Ca2+]i elicited by the three ETs (ET-1, ET-2, and ET-3) were transient and did not show a sustained phase. Chelating extracellular Ca2+ in the medium by adding excess EGTA decreased the ET-mediated Ca2+ response by 40-50%. This result indicates that a substantial portion of the increase in [Ca2+]i was due to influx from an extracellular source. However, the increase in [Ca2+]i was not affected by verapamil or nifedipine (10(-5) M). A rank order potency of ET-1 > ET-2 > ET-3 is shown for the stimulated increase in [Ca2+]i, as well as labeled inositol phosphates, in these cells. ATP (10(-4) M) and bradykinin (10(-7) M) also induced the increases in [Ca2+]i and Ins(1,4,5)P3 in NG108-15 cells, albeit to a different extent. When compared at 10(-7) M, bradykinin elicited a five- to sixfold higher increase in the level of Ins(1,4,5)P3, but less than a twofold higher increase in [Ca2+]i than those induced by ET-1. Additive increases in both Ins(1,4,5)P3 and [Ca2+]i were observed when ET-1, ATP, and bradykinin were added to the cells in different combinations, suggesting that each receptor agonist is responsible for the hydrolysis of a pool of polyphosphoinositide within the membrane. ET-1 exhibited homologous desensitization of the Ca2+ response, but partial heterologous desensitization to the Ca2+ response elicited by ATP. On the contrary, ET-1 did not desensitize the response elicited by bradykinin, although bradykinin exhibited complete heterologous desensitization to the response elicited by ET-1. Taken together, these results illustrate that, in NG108-15 cells, a considerable amount of receptor cross talk occurs between ET and other receptors that transmit signals through the polyphosphoinositide pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Bradykinin / pharmacology*
  • Calcium / metabolism*
  • Calcium Channels*
  • Egtazic Acid / pharmacology
  • Endothelins / pharmacology*
  • Fura-2
  • Glioma
  • Hybrid Cells
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors
  • Kinetics
  • Neuroblastoma
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols / metabolism
  • Radioligand Assay
  • Receptors, Cell Surface / metabolism
  • Receptors, Cytoplasmic and Nuclear*
  • Time Factors

Substances

  • Calcium Channels
  • Endothelins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Egtazic Acid
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • Bradykinin
  • Calcium
  • Fura-2