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The three α2-adrenergic receptor subtypes have distinct tissue distributions, desensitization properties, and, in some cell types, subtype-specific subcellular localization and trafficking properties. The subtypes also differ in their neuronal physiology. Therefore, we have investigated the localization and targeting of human α2-adrenoceptors (α2-AR) in PC12 cells, which were transfected to express the α2-AR subtypes A, B, and C. Inspection of the receptors by indirect immunofluorescence and confocal microscopy showed that α2A-AR were mainly targeted to the tips of the neurites, α2B-AR were evenly distributed in the plasma membrane, and α2C-AR were mostly located in an intracellular perinuclear compartment. After agonist treatment, α2A- and α2B-AR were internalized into partly overlapping populations of intracellular vesicles. Receptor subtype-specific changes in PC12 cell morphology were also discovered: expression of α2A-AR, but not of α2B- or α2C-AR, induced differentiation-like changes in cells not treated with NGF. Also α2B-AR were targeted to the tips of neurites when they were coexpressed in the same cells with α2A-AR, indicating that the targeting of receptors to the tips of neurites is a consequence of a change in PC12 cell membrane protein trafficking that the α2A-subtype induces. The marked agonist-induced internalization of α2A-AR observed in both nondifferentiated and differentiated PC12 cells contrasts with earlier results from non-neuronal cells and points out the importance of the cellular environment for receptor endocytosis and trafficking. The targeting of α2A-AR to nerve terminals in PC12 cells is in line with the putative physiological role of this receptor subtype as a presynaptic autoreceptor.

Receptor Subtype-Induced Targeting and Subtype-Specific Internalization of Human α2-Adrenoceptors in PC12 Cells

Receptor Subtype-Induced Targeting and Subtype-Specific Internalization of Human α₂-Adrenoceptors in PC12 Cells