Widespread distribution of orexin in rat brain and its regulation upon fasting.

Orexins A and B, novel hypothalamic peptides encoded by a single mRNA transcript, stimulate food intake. Two antisera specific for the individual rat orexins were prepared and sensitive RIAs developed. Orexin-A and -B are abundant in the rat hypothalamus, medulla-pons, and midbrain-thalamus, and moderately abundant in the cerebral cortex. No orexins were found in the adipose tissues or visceral organs studied. The major endogenous molecule of orexin-A is a 33-amino-acid peptide, and that of orexin-B a 28-amino-acid peptide. After a 48 h fast, the orexin-A and -B contents of the lateral hypothalamus exhibited a trend to increase, but the contents of other brain tissues significantly decreased as compared with the fed control rats. No circadian variations in the orexin contents were found in the brain. The extensive and abundant distribution of orexins in the brain and changes in their contents upon fasting suggest that they serve as neuromodulators and/or neurotransmitters that regulate feeding behavior through interaction with diverse neural networks.