In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 17, No. 13 ( 1997-07-01), p. 4956-4964
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 Gβγ 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 α 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 agonist 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 βγ subunits are the relevant signal transducers for A 1 receptor-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 A 1 receptors is the release of βγ 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.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.17-13-04956.1997
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
1997
detail.hit.zdb_id:
1475274-8
SSG:
12
Bookmarklink