Effects of minocycline on accumulation of cyclic AMP in cerebral cortex of rat. A comparison with lithium.
The tetracycline minocycline and lithium have been reported to share some biochemical properties. This study was aimed at investigating the effects of minocycline and lithium in vitro on accumulation of noradrenaline-, forskolin- and calcium-(Ca2+) stimulated cyclic AMP (cAMP) in the cerebral cortex of the rat. Minocycline and lithium dose-dependently inhibited noradrenaline-stimulated formation of cAMP in slices of cortex, but only lithium inhibited the formation of cAMP induced by forskolin. In contrast to lithium, minocycline did not affect either noradrenaline- or Ca(2+)-stimulated activity of adenylate cyclase in a preparation of cortical membranes. However, in slices of cortex ouabain-induced formation of cAMP (dependent on extracellular Ca2+ and blocked by the Ca2+ channel antagonist, verapamil) was reduced both by minocycline and lithium. The present results indicate that the mechanisms of action of minocycline and lithium on the cAMP signalling system in the brain of the rat differ. Minocycline does not seem to interact directly with the adenylate cyclase, as reported for lithium. The decreased agonist-stimulated production of cAMP in intact cells, in the presence of minocycline, might be due to the ability of minocycline to chelate Ca2+ ions.
Mørk
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Department of Pharmacology, Panum Institute, University of Copenhagen, Denmark.
Geisler
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D005576:Colforsin; D010042:Ouabain; D008094:Lithium; D014700:Verapamil; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008911:Minocycline; D002118:Calcium; D009638:Norepinephrine