ADENOSINE A(1) RECEPTOR-MEDIATED ACTIVATION OF PHOSPHOLIPASE-C IN CULTURED ASTROCYTES DEPENDS ON THE LEVEL OF RECEPTOR EXPRESSION

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 phospholipas e C (PLC) results in a synergistic potentiation of PLC activity. Evide nce has accumulated that G beta gamma subunits mediate this potentiati ng effect, However, an A(1) receptor-mediated increase in extracellula r glutamate was suggested to be responsible for the potentiating effec t in mouse astrocyte cultures. We have investigated the synergistic ac tivation 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) recepto r mRNA as well as receptor protein is present in astrocytes from all b rain regions, (2) A(1) receptor-mediated inhibition of adenylyl cyclas e is of similar extent in all astrocyte cultures, (3) the A(1) recepto r-mediated potentiation of PLC activity requires higher concentrations of agonise than adenylyl cyclase inhibition and is dependent on the e xpression level of A(1) receptor, and (4) the potentiating effect on P LC activity is unrelated to extracellular glutamate. Taken together, o ur data support the notion that beta gamma subunits are the relevant s ignal transducers for A(1) receptor-mediated PLC activation in rat ast rocytes. 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) rec eptors is the release of beta gamma subunits via G(i/o) activation suf ficient to stimulate PLC. It is concluded that variation of the expres sion level of adenosine A(1) receptors may be an important regulatory mechanism to control PLC activation via this receptor.