The 'serotonin/norepinephrine link' beyond the beta adrenoceptor.
C6 rat glioma cells were utilized as a model system to probe the 'serotonin/norepinephrine link' at the level of preproenkephalin (PPE) gene expression. The beta adrenoceptor mediated increase in PPE mRNA was attenuated by the selective beta 1 adrenoceptor antagonist metoprolol which blocked the isoproterenol induced cyclic AMP generation by 97%. The subtype nonspecific antagonist propranolol blocked both the isoproterenol induced increase in cyclic AMP and the increase in the PPE mRNA steady-state levels. Serotonin (5-HT) had no effect on the density of beta adrenoceptors or their down-regulation by isoproterenol and did not alter the PPE gene expression in the absence of the beta signal. However, 5-HT significantly deamplified the beta signal mediated enhancement of the PPE mRNA thus indicating that the aminergic link occurs beyond the beta adrenoceptor.
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232.
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A
Eiring
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Manier
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PR
Bieck
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RD
Howells
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Sulser
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005910:Glioma; D005938:Glucocorticoids / Q000235:genetics*; D008954:Models, Biological; D009638:Norepinephrine / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012701:Serotonin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000319:Adrenergic beta-Antagonists; D004745:Enkephalins; D005938:Glucocorticoids; D011498:Protein Precursors; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; C033660:preproenkephalin; D000242:Cyclic AMP; D009638:Norepinephrine