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.