Characterization of orexin-A and orexin-B in the microdissected rat brain nuclei and their contents in two obese rat models

Orexin-A and orexin-B (also known as hypocretins) are newly discovered hypo thalamic peptides that stimulate food intake. Using separate radioimmunoass ays for these rat orexins, we determined their distributions in microdissec ted nuclei of the diencephalon and brainstem which have accumulations of or exin fibers. High orexin contents (orexin-A: between 250 and 350 fmol/mg pr otein and orexin-B: between 650 and 900 fmol/mg protein) were present in th e lateral hypothalamus; ventromedial hypothalamic, paraventricular thalamic and dorsal raphe nuclei; periaqueductal central gray and locus coeruleus. Moderate orexin contents (orexin-A: between 100 and 250 fmol/mg protein and orexin-B: between 300 and 500 fmol/mg protein) were found in the median em inence; suprachiasmatic, paraventricular hypothalamic, arcuate and supraopt ic nuclei; substantia nigra and the nucleus of the solitary tract. Mature o rexin-A and -B peptides were the major endogenous orexin molecules in these nuclei. The orexin-A and -B contents in the brains of obese Zucker rats th at have disrupted leptin receptor were significantly higher than in their l ean littermates, but in Otsuka Long-Evans Tokushima Fatty rats that have di srupted cholecystokinin type-A receptor the contents were similar to those of the controls. The widespread orexin distributions in the nuclei of dienc ephalon and brainstem suggest that orexins serve as neuromodulators, neurot ransmitters, or both, in a wide variety of neural networks that regulate th e autonomic and neuroendocrine systems. (C) 1999 Elsevier Science Ireland L td. All rights reserved.