Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. A modulation effect on luteinizing hormone-releasing hormone (LHRH) secretion also suggests a more minor contribution to the regulation of reproductive function. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity. Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses. Produced by a small group of neurons restricted to the lateral and posterior hypothalamus and perifornical areas. Positive neurons project widely throughout the entire neuroaxis. Particularly abundant projections in the cerebral cortex, olfactory bulb, hippocampus, amygdala, septum, diagonal band of Broca, bed nucleus of the stria terminalis, thalamus, anterior and posterior hypothalamus, midbrain, brainstem, and spinal cord. Immunoreactivity reported in the enteric nervous system and pancreas. In small amount, also detected in the testis. Detected as early as embryonic day 18, but expression increased dramatically after the third postnatal week. By nutritional state, up-regulated by fasting, fluid deprivation and insulin-induced hypoglycemia. Orexin-A immunoreactivity varies diurnally and peaks during the dark phase, in the pons and the location of locus coeruleus. Specific enzymatic cleavages at paired basic residues yield the different active peptides. Belongs to the orexin family. Qui dort dine - Issue 15 of October 2001