[Desipramine-induced down regulation of beta-adrenergic receptors: effects of noradrenergic and serotonergic neuronal activities and of alpha 2-adrenergic receptor mediated mechanisms].
The mechanisms of antidepressant (desipramine)-induced down regulation of beta-adrenergic receptors were investigated. The number of beta-adrenergic receptors in rat cerebral cortex was increased by the destruction of norepinephrine (NE) neurons with 6-hydroxydopamine or DSP-4 pretreatments. Desipramine (DMI)-induced down regulation of beta-receptors was completely prevented by these procedures, whereas the destruction of serotonin (5-HT) neurons neither changed the receptor number nor prevented the DMI-induced down regulation. The number of beta-adrenergic receptors showed a decrease within 3 days by treatment of DMI plus (+) mianserin or yohimbine which promotes NE and 5-HT release from nerve endings through presynaptic alpha 2-adrenergic antagonism. Another alpha 2-adrenergic antagonist (-)mianserin, which promotes only 5-HT release, also accelerated the down regulation induced by DMI, but this acceleration was not prevented by the destruction of 5-HT neurons. Combination of DMI with 5-HT releasing agent methiothepin (5-HT autoreceptor antagonist) did not accelerate beta-receptor down regulation. These results suggest that 1) NE availability in the synaptic cleft plays a significant role in the regulation of beta-receptor number, but 2) postsynaptic alpha 2-adrenergic mechanisms also seem to contribute to the regulation, whereas 3) 5-HT neurons have no significant effect on the process.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*
D000928:Antidepressive Agents; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D003891:Desipramine; D009638:Norepinephrine