Adenosine A1Receptor-Mediated Activation of Phospholipase C in Cultured Astrocytes Depends on the Level of Receptor Expression
Open Access
- 1 July 1997
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 17 (13), 4956-4964
- https://doi.org/10.1523/jneurosci.17-13-04956.1997
Abstract
Adenosine A1receptors induce an inhibition of adenylyl cyclase via G-proteins of the Gi/ofamily. In addition, simultaneous stimulation of A1receptors and of receptor-mediated activation of phospholipase C (PLC) results in a synergistic potentiation of PLC activity. Evidence has accumulated that Gβγ subunits mediate this potentiating effect. However, an A1receptor-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 A1and α1adrenergic receptors in primary cultures of astrocytes derived from different regions of the newborn rat brain. It is reported here that (1) adenosine A1receptor mRNA as well as receptor protein is present in astrocytes from all brain regions, (2) A1receptor-mediated inhibition of adenylyl cyclase is of similar extent in all astrocyte cultures, (3) the A1receptor-mediated potentiation of PLC activity requires higher concentrations of agonist than adenylyl cyclase inhibition and is dependent on the expression level of A1receptor, and (4) the potentiating effect on PLC activity is unrelated to extracellular glutamate.Taken together, our data support the notion that βγ subunits are the relevant signal transducers for A1receptor-mediated PLC activation in rat astrocytes. Because of the lower affinity of βγ, as compared with α subunits, more βγ subunits are required for PLC activation. Therefore, only in cultures with higher levels of adenosine A1receptors is the release of βγ subunits via Gi/oactivation sufficient to stimulate PLC. It is concluded that variation of the expression level of adenosine A1receptors may be an important regulatory mechanism to control PLC activation via this receptor.Keywords
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