Update on neuroreceptor mechanisms and their implication for the pharmacotherapy of affective disorders.
Unlike "acceptors" (binding sites), receptors for neurohormones display the dual function of recognition and biologic response via coupling to effector systems that generate second messengers or to ion channels that modify the passage of specific ions. The demonstration that membrane receptors for norepinephrine are coupled in a stimulatory (beta 1, beta 2) or inhibitory (alpha 2) way via nucleotide regulatory proteins to adenylate cyclase, thus increasing or decreasing the formation of the second messenger cyclic AMP, is discussed. Serotonin receptors are linked to phosphatidylinositol hydrolysis generating two second messengers, diacylglycerol and inositol triphosphate. Pharmacologically, serotonin (5-HT) receptors that are linked to phosphatidylinositol hydrolysis are of the 5-HT2 type in the cerebral cortex and of the 5-HT1c type in the choroid plexus. The final common pathway of signal transduction appears to be the protein-kinase-mediated phosphorylation of cellular proteins. Glucocorticoid receptors have been found to be located in the cytoplasma or nuclei of aminergic cell bodies and may exert their effects by modifying the genomic expression of the respective neurons. The two aminergic receptor systems are biomolecularly linked, with glucocorticoids exerting a modulatory role. The implications of central receptor research for the pharmacotherapy and the pathophysiology of affective disorders are reviewed.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*
D000928:Antidepressive Agents; D017981:Receptors, Neurotransmitter