Regulation and function of noradrenaline receptor systems in brain. Psychopharmacological aspects.
Central beta-adrenoceptors are coupled to adenylate cyclase in a stimulatory manner. However, there is only circumstantial evidence that alpha 2-adrenoceptors in brain are coupled to adenylate cyclase in an inhibitory manner. The desensitization of the beta-adrenoceptor system induced by antidepressants seems to be a common action of clinically effective antidepressants. alpha 2-Adrenoceptor subsensitivity, if it occurs following administration of some antidepressants, contributes to the development of down-regulation of beta-adrenoceptors. The occupancy of adrenoceptors by noradrenaline (NA) is a prerequisite for both desensitization of the system and the reduction in the number of beta-adrenoceptors while serotonin (5-HT) is co-required with NA for the regulation of the density of beta-adrenoceptors. The decrease in the number of beta-adrenoceptors induced by antidepressants is rapidly reversible following inhibition of 5-HT synthesis by p-chlorophenylalanine. Since beta-adrenoceptor-coupled adenylate cyclase systems function as kinetic amplification systems, small changes in the NA signal transfer are amplified or deamplified respectively. beta-Adrenoceptors may also subserve a critical role in neuronal membranes by determining the sensitivity of other membrane receptor systems.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D002490:Central Nervous System / Q000502:physiology; D006801:Humans; D008566:Membranes / Q000378:metabolism; D009638:Norepinephrine / Q000502:physiology; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology
D000928:Antidepressive Agents; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D009638:Norepinephrine