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.
Eiring
A
A
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232.
Manier
D H
DH
Bieck
P R
PR
Howells
R D
RD
Sulser
F
F
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