Adenosine A(1) receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression

K Biber, KN Klotz, M Berger, PJ GebickeHarter, D vanCalker

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Abstract

Adenosine A(1) receptors induce an inhibition of adenylyl cyclase via G-proteins of the G(i/o) family. In addition, simultaneous stimulation of A(1) receptors and of receptor-mediated activation of phospholipase C (PLC) results in a synergistic potentiation of PLC activity. Evidence has accumulated that G beta gamma subunits mediate this potentiating effect, However, an A(1) receptor-mediated increase in extracellular glutamate was suggested to be responsible for the potentiating effect in mouse astrocyte cultures. We have investigated the synergistic activation of PLC by adenosine A(1) and alpha(1) adrenergic receptors in primary cultures of astrocytes derived from different regions of the newborn rat brain. It is reported here that (1) adenosine A(1) receptor mRNA as well as receptor protein is present in astrocytes from all brain regions, (2) A(1) receptor-mediated inhibition of adenylyl cyclase is of similar extent in all astrocyte cultures, (3) the A(1) receptor-mediated potentiation of PLC activity requires higher concentrations of agonise than adenylyl cyclase inhibition and is dependent on the expression level of A(1) receptor, and (4) the potentiating effect on PLC activity is unrelated to extracellular glutamate.

Taken together, our data support the notion that beta gamma subunits are the relevant signal transducers for A(1) receptor-mediated PLC activation in rat astrocytes. Because of the lower affinity of beta gamma, as compared with oc subunits, more beta gamma subunits are required for PLC activation. Therefore, only in cultures with higher levels of adenosine A(1) receptors is the release of beta gamma subunits via G(i/o) activation sufficient to stimulate PLC. It is concluded that variation of the expression level of adenosine A(1) receptors may be an important regulatory mechanism to control PLC activation via this receptor.

Original languageEnglish
Pages (from-to)4956-4964
Number of pages9
JournalThe Journal of Neuroscience
Volume17
Issue number13
Publication statusPublished - 1-Jul-1997

Keywords

  • inhibitory G-protein
  • beta gamma subunits
  • inositol phosphates
  • rat astrocytes
  • phospholipase C
  • adenosine A(1) receptor coupling
  • RT-PCR
  • receptor binding
  • SMOOTH-MUSCLE CELLS
  • BETA-GAMMA-SUBUNITS
  • G-PROTEINS
  • CYCLIC-AMP
  • CROSS-TALK
  • INOSITOL 1,4,5-TRISPHOSPHATE
  • INTRACELLULAR CALCIUM
  • MUSCARINIC-RECEPTOR
  • SIGNAL-TRANSDUCTION
  • ADENYLYL-CYCLASE

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