Stress-induced intracellular trafficking of corticotropin-releasing factor receptors in rat locus coeruleus neurons.
Corticotropin-releasing factor (CRF) activates locus coeruleus (LC)-norepinephrine neurons during stress. Previous stress or CRF administration attenuates the magnitude of this response by decreasing postsynaptic sensitivity to CRF. Here we describe the fate of CRF receptors (CRFr) in LC neurons after stress. Rats were exposed to swim stress or handling and perfused 1 or 24 h later. Sections through the LC were processed for immunogold-silver labeling of CRFr. CRFr in LC dendrites was present on the plasma membrane and within the cytoplasm. In control rats, the ratio of cytoplasmic to total dendritic labeling was 0.55 +/- 0.01. Swim stress increased this ratio to 0.77 +/- 0.01 and 0.80 +/- 0.02 at 1 and 24 h after stress, respectively. Internalized CRFr was associated with different organelles at different times after stress. At 1 h after stress, CRFr was often associated with early endosomes in dendrites and perikarya. By 24 h, more CRFr was associated with multivesicular bodies, suggesting that some of the internalized receptor is targeted for degradation. In perikarya, more internalized CRFr was associated with Golgi apparatus 24 vs. 1 h after stress. This is suggestive of changes in CRFr synthesis. Alternatively, this may indicate communication between multivesicular bodies and Golgi apparatus in the process of recycling. Administration of the selective CRF(1) antagonist, antalarmin, before swim stress attenuated CRFr internalization. The present demonstration of stress-induced internalization of CRFr in LC neurons provides evidence that CRF is released in the LC during swim stress to activate this system and initiate cellular trafficking of the receptor that determines subsequent sensitivity of LC neurons to CRF.
Reyes
Beverly A S
BA
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA. bsr103@jefferson.edu
Valentino
Rita J
RJ
Van Bockstaele
Elisabeth J
EJ
D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D013550:Swimming; D014018:Tissue Distribution; D000099052:CRF Receptor, Type 1
D006727:Hormone Antagonists; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone