Ca2+ dependent purinergic regulation of p42 and p44 MAP kinases in astroglial cultured cells

Biomed Pharmacother. 1998;52(4):180-6. doi: 10.1016/s0753-3322(98)80208-4.

Abstract

Adenosine triphosphate (ATP) is a signaling molecule for brain cells including astrocytes. In these cells, it has been shown that ATP stimulates myelin basic protein (MBP) kinase activity which is believed to represent the Erk family of MAP kinases. Indeed, we show that ATP activates simultaneously MBP kinase activity and phosphotyrosine incorporation in p42 Erk2 and p44 Erk1. Maximal effect of ATP is obtained at 50 microM after 5 min and disappears after 60 min. Effect of ATP is mimicked by 2-methylthio-ATP whereas alpha beta-methyleneadenosine 5' triphosphate (AMP-CPP) and adenosine do not promote any effect. Uridine triphosphate (UTP) activates also p42 and p44 MAP kinases. These observations indicate that p42-p44 MAP kinases activation can be obtained through P2v and P2u receptors. Purinergic stimulation of Erk is insensitive to pertussis toxin which inactivates heterotrimeric Gi protein. It is not inhibited by a PLA2 inhibitor (4 bromophenacyl bromide [B phi B]) and the PI3 kinase inhibitor, wortmannin. In contrast, purinergic stimulation of Erk is partially inhibited by the PKC inhibitor. GF109203X, at 5 microM and suppressed when extracellular calcium is complexed by ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / pharmacology*
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Brain / cytology
  • Brain / metabolism*
  • Calcium / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cells, Cultured
  • Egtazic Acid / pharmacology
  • Kinetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / physiology*
  • Uridine Triphosphate / pharmacology

Substances

  • Adenine Nucleotides
  • Receptors, Purinergic P2
  • Egtazic Acid
  • Adenosine Triphosphate
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Calcium
  • Uridine Triphosphate