Developmental expression and regulation of alpha 1 adrenergic receptors in cultured cortical neurons.
The expression and distribution of alpha 1 receptors in cultured neurons derived from rat visual cortex were studied with confocal microscopy using the fluorescently labeled alpha 1 adrenergic receptor selective antagonist BODIPY FL prazosin. The receptors were found to be clustered on neuronal somata and on proximal dendrites. We found that expression of the alpha 1 receptor is regulated both by neuronal excitability and by the usage of the receptor itself. The specificity of receptor regulation to the blockade of a particular receptor class was also studied. We approached this by comparing the effects of treatment with the alpha 1 adrenoreceptor antagonist prazosin and M1 muscarinic receptor antagonist pirenzepine on the expression of alpha 1 and M1 receptors in cultured cortical neurons. The results showed that blockade of muscarinic receptors with pirenzepine up-regulated muscarinic receptor expression selectively without changing alpha 1 receptor expression. Conversely blockade of alpha 1 receptors up-regulated alpha 1 expression but not muscarinic receptor expression. This implies that the expression levels of M1 and alpha 1 receptors are both regulated through specific signal transduction pathways. The interactions between neuronal activity and receptor activation (or blockade) on receptor expression were studied as well. In these experiments we compared the effects of high K+, tetrodotoxin (TTX), prazosin, and noradrenaline on the expression of alpha 1 and M1 receptors in cultured neurons. The results show that high K+ exposure increased both alpha 1 and M1 receptor expression regardless of the presence of receptor agonists or antagonists. On the other hand, TTX exposure reduced both alpha 1 and M1 receptor expression regardless of the presence of the receptor agonists or antagonists. This implies that regulation of receptor number is predominantly regulated by neuronal activity rather than by receptor occupancy.
Wang
Y
Y
Department of Ophthalmology, University of British Columbia, Vancouver, Canada.
Gu
Q
Q
Mao
F
F
Cynader
M S
MS
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology*
D005456:Fluorescent Dyes; D018340:Receptors, Adrenergic, alpha-1