Inactivation of cyclic AMP-dependent taurine release from astroglia.
When astroglial cells are exposed to beta-adrenergic agonists for long periods of time (greater than 20 min), transient increases in taurine release and intracellular cyclic AMP (cAMP) are observed. Three phases of taurine release can be distinguished: activation, inactivation, and an elevated steady state. In this article, we present data describing the relationship between intracellular cAMP levels and inactivation of taurine release. To do this, we compared the apparent first-order rate constants for the inactivation of taurine release (ktau) with the apparent first-order rate constant for the decline of intracellular cAMP (kcAMP). We also measured ktau under experimental conditions that were chosen to provide a wide range of intracellular cAMP concentrations or to stimulate release without the involvement of the beta-adrenergic receptor and adenylate cyclase. When taurine release was stimulated with a saturating concentration of isoproterenol, the inactivation of release was significantly faster than the decline of intracellular cAMP. Furthermore, there were no significant differences in ktau measured under any of the experimental conditions used. Thus, inactivation of taurine release does not involve changes in the activity of the beta-adrenergic receptor and adenylate cyclase, i.e., desensitization, and appears to be independent of the intracellular concentration of cAMP. These results indicate that cAMP-mediated events can be regulated by mechanism(s) in addition to those that control receptor-adenylate cyclase interactions and the synthesis of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Shain
W
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Laboratory of Neurotoxicology and Nervous System Disorders, Wadsworth Center for Laboratories and Research, Albany NY 12201.
Madelian
V
V
Martin
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DL
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013654:Taurine / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D013654:Taurine; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003994:Bucladesine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol