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Chromaffin cells probably are the most intensively studied of the neural crest derivates. They are closely related to the nervous system, share with neurons some fundamental mechanisms and thus were the ideal model to study the basic mechanisms of neurobiology for many years. The lessons we have learned from chromaffin cell biology as a peripheral model for the brain and brain diseases pertain more than ever to the cutting edge research in neurobiology. Here, we highlight how studying this cell model can help unravel the basic mechanisms of cell renewal and regeneration both in the central nervous system (CNS) and neuroendocrine tissue and also can help in designing new strategies for regenerative therapies of the CNS.

Both constitutive and inducible interleukin-1 (IL-1) gene expressions have been described in the central nervous system, the former being associated with immunoreactive IL-1 neurons in human and rat hypothalami. While most studies have focused on the role of IL-1 as a mediator of pathological events in the brain, the cytokine of neuronal origin might also be involved in the regulation of physiological processes. In this study we used a previously validated technique to investigate the effects of classical neurotransmitters and the hypophysiotropic peptide corticotropin-releasing hormone (CRH) on the release of immunoreactive (ir) IL-1 beta from acute rat hypothalamic explants. We found that basal irIL-1 beta secretion is significantly inhibited by acetylcholine and histamine and increased by dopamine, while dexamethasone, IL-4 and IL-10 have no effect. Moreover, cytokine release is dose-dependently increased by CRH. Such effects of the neurotransmitters and CRH are observed in short-term incubation experiments, indicating that a pre-formed pool of hypothalamic IL-1 beta is involved. These findings also suggest that the interaction between IL-1, neurotransmitters and neuropeptides might play a role in the physiological regulation of such processes as body temperature, food intake and the control of hypothalamic-hypophyseal axes.

Although recent evidence suggests that the gas nitric oxide (NO) can modulate the secretion of corticotropin-releasing hormone (CRH) from acute rat hypothalamic explants, another gas, carbon monoxide (CO), has been suggested to play a role in neural signaling in the brain; CO may complement the activity of NO in long term potentiation. In this study, we have investigated whether CO shares with NO the ability to modify the release of CRH from the rat hypothalamus. Hemin, a specific CO precursor through the enzyme heme oxygenase (the enzymatic pathway synthesizing endogenous CO), was found to inhibit in a dose-dependent manner KCl-stimulated CRH release, with a maximal effect at 1 microM, while showing no effect on basal CRH secretion. The stimulation of CRH by interleukin-1 beta (100 ng/ml) was also significantly antagonized by hemin (1 microM). An inhibitor of heme oxygenase, zinc-protoporphyrin-9, had no effect on basal or stimulated CRH release up to a maximal dose of 10 microM. When hemin and zinc-protoporphyrin-9 were given together, the hemin-induced inhibition of CRH release was completely antagonized by the enzyme inhibitor. These findings provide evidence that endogenous CO may play a role in the control of CRH release; by analogy with NO, CO may represent a major new neuroendocrine modulator. © 1994 by The Endocrine Society.