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Volume 17, Number 13, Issue of July 1, 1997 pp. 4956-4964
Copyright ©1997 Society for Neuroscience

Adenosine A₁ Receptor-Mediated Activation of Phospholipase C in Cultured Astrocytes Depends on the Level of Receptor Expression

Received Feb. 18, 1997; revised April 11, 1997; accepted April 14, 1997.

Knut Biber^{1, 2}, Karl-Norbert Klotz³, Mathias Berger¹, Peter J. Gebicke-Härter¹, and Dietrich van Calker¹

¹ Department of Psychiatry, University of Freiburg, D-79104 Freiburg, Germany, ² Institute for Biology II, University of Freiburg, D-79104 Freiburg, Germany, and ³ Institute for Pharmacology and Toxicology, University of Würzburg, D-97078 Würzburg, Germany

Adenosine A₁ receptors induce an inhibition of adenylyl cyclase via G-proteins of the G_i/o family. In addition, simultaneous stimulation of A₁ receptors and of receptor-mediated activation of phospholipase C (PLC) results in a synergistic potentiation of PLC activity. Evidence has accumulated that G subunits mediate this potentiating effect. However, an A₁ 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 A₁ and ₁ adrenergic receptors in primary cultures of astrocytes derived from different regions of the newborn rat brain. It is reported here that (1) adenosine A₁ receptor mRNA as well as receptor protein is present in astrocytes from all brain regions, (2) A₁ receptor-mediated inhibition of adenylyl cyclase is of similar extent in all astrocyte cultures, (3) the A₁ receptor-mediated potentiation of PLC activity requires higher concentrations of agonist than adenylyl cyclase inhibition and is dependent on the expression level of A₁ receptor, and (4) the potentiating effect on PLC activity is unrelated to extracellular glutamate.

Taken together, our data support the notion that subunits are the relevant signal transducers for A₁ receptor-mediated PLC activation in rat astrocytes. Because of the lower affinity of , as compared with  subunits, more subunits are required for PLC activation. Therefore, only in cultures with higher levels of adenosine A₁ receptors is the release of subunits via G_i/o activation sufficient to stimulate PLC. It is concluded that variation of the expression level of adenosine A₁ receptors may be an important regulatory mechanism to control PLC activation via this receptor.

Key words: inhibitory G-protein; subunits; inositol phosphates; rat astrocytes; phospholipase C; adenosine A₁ receptor coupling; RT-PCR; receptor binding

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