Adenosine stimulates cAMP-mediated taurine release from LRM55 glial cells.
The possible role of adenosine as a modulator or transmitter in the central nervous system was tested by measuring its effects on LRM55 astroglial cells. Two related cellular responses were measured--receptor activated increases in intracellular cAMP and cAMP-mediated taurine release. Taurine is a neuroinhibitory amino acid that is taken up, stored, and released from primary cultures of astrocytes and astroglial cells. Three-minute incubations of cells with adenosine caused a dose-dependent accumulation of intracellular cAMP and release of the taurine (EC50 = 5.0 x 10(-5) M and 1.6 x 10(-6) M, respectively). That the cellular responses were mediated through the activation of specific adenosine receptors was indicated by the observations that the adenosine receptor antagonist isobutylmethylxanthine (IBMX) but not the beta-adrenergic receptor antagonist 1-propranolol inhibited responses to adenosine. The study of various adenosine analogs showed a rank order of potency (chloroadenosine = 5'-(N-ethyl)carboxamido-adenosine greater than N6-(L-2-phenylisopropyl)-adenosine greater than cyclohexyladenosine = cyclopentyladenosine) characteristic of the low affinity A2-type adenosine receptors that have been associated with cAMP elevation in several tissues. These results indicate that, in addition to directly affecting neurons, adenosine may have a primary site of action on astroglial cells resulting in taurine release and subsequent inhibition of neuronal activity.
Madelian
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V
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Silliman
S
S
Shain
W
W
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013654:Taurine / Q000378:metabolism*
D013654:Taurine; D011433:Propranolol; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine