Modulation of receptor-mediated cyclic AMP production in brain.
Alpha-Adrenergic and GABAB receptor agonists regulate adenylate cyclase either negatively, by direct inhibition of the enzyme, or positively, by augmenting agonist-stimulated production of cyclic AMP. While the inhibition of adenylate cyclase is most likely to be mediated by a direct stimulation of Gi protein, the enhancement of production of cyclic nucleotide appears to involve protein kinase C and perhaps PLA2. alpha-Adrenergic and GABAB receptor augmentation of accumulation of cyclic AMP is also influenced by pituitary-adrenal hormones, suggesting a link between brain function and the endocrine system. The number of components associated with the modulation of neurotransmitter receptor-coupled second messenger production provides multiple targets for the pharmacological manipulation of this system. By influencing the modulatory response rather than receptor activity directly, it may be possible to produce subtle alterations in the function of the central nervous system yielding safer and perhaps more effective therapies for the treatment of mental illness.
Duman
R S
RS
Abraham Ribicoff Research Facilities, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
Enna
S J
SJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism
D000928:Antidepressive Agents; D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D017981:Receptors, Neurotransmitter; D000242:Cyclic AMP; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D000262:Adenylyl Cyclases; D002118:Calcium