%0 Journal Article %1 Biber1997 %A Biber, K. %A Klotz, K. N. %A Berger, M. %A Gebicke-Harter, P. J. %A van Calker, D. %D 1997 %J J Neurosci %K & AMP/biosynthesis Activation Adenosine/analogs Adenylate Adrenergic Animals Astrocytes/*metabolism Bordetella/pharmacology Brain/cytology/metabolism C Cultured Cyclase Cyclic Enzyme Extracellular Factors, Glutamates/antagonists Inositol Messenger/metabolism P1/genetics/*physiology Peptides Phosphates/biosynthesis Phospholipases/*metabolism Purinergic RNA, Rats Space/metabolism Toxin Type Venoms/pharmacology Virulence Wasp Xanthines/metabolism alpha-Agonists/pharmacology alpha/physiology derivatives/pharmacology inhibitors/metabolism Receptor Cell %N 13 %P 4956-64 %T Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9185533 %V 17 %X Adenosine A1 receptors induce an inhibition of adenylyl cyclase via G-proteins of the Gi/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 Gbetagamma 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 alpha1 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 betagamma subunits are the relevant signal transducers for A1 receptor-mediated PLC activation in rat astrocytes. Because of the lower affinity of betagamma, as compared with alpha subunits, more betagamma subunits are required for PLC activation. Therefore, only in cultures with higher levels of adenosine A1 receptors is the release of betagamma subunits via Gi/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.

@article{Biber1997, abstract = {Adenosine A1 receptors induce an inhibition of adenylyl cyclase via G-proteins of the Gi/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 Gbetagamma 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 alpha1 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 betagamma subunits are the relevant signal transducers for A1 receptor-mediated PLC activation in rat astrocytes. Because of the lower affinity of betagamma, as compared with alpha subunits, more betagamma subunits are required for PLC activation. Therefore, only in cultures with higher levels of adenosine A1 receptors is the release of betagamma subunits via Gi/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.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Biber, K. and Klotz, K. N. and Berger, M. and Gebicke-Harter, P. J. and van Calker, D.}, biburl = {https://www.bibsonomy.org/bibtex/235bcbb545d369d7beb372a31adedd8a1/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {7fdbab810d0168d3baab3b2de5d78aa1}, intrahash = {35bcbb545d369d7beb372a31adedd8a1}, issn = {0270-6474 (Print) 0270-6474 (Linking)}, journal = {J Neurosci}, keywords = {& AMP/biosynthesis Activation Adenosine/analogs Adenylate Adrenergic Animals Astrocytes/*metabolism Bordetella/pharmacology Brain/cytology/metabolism C Cultured Cyclase Cyclic Enzyme Extracellular Factors, Glutamates/antagonists Inositol Messenger/metabolism P1/genetics/*physiology Peptides Phosphates/biosynthesis Phospholipases/*metabolism Purinergic RNA, Rats Space/metabolism Toxin Type Venoms/pharmacology Virulence Wasp Xanthines/metabolism alpha-Agonists/pharmacology alpha/physiology derivatives/pharmacology inhibitors/metabolism Receptor Cell}, month = {Jul 1}, note = {Biber, K Klotz, K N Berger, M Gebicke-Harter, P J van Calker, D Research Support, Non-U.S. Gov't United states The Journal of neuroscience : the official journal of the Society for Neuroscience J Neurosci. 1997 Jul 1;17(13):4956-64.}, number = 13, pages = {4956-64}, shorttitle = {Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression}, timestamp = {2010-12-14T18:22:38.000+0100}, title = {Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9185533}, volume = 17, year = 1997 }