Actions of secretin on the hypothalamic magnocellular neurons: Implications for the control of body water homostasis

Abstract

For the last 100 years, secretin has been extensively studied for its hormonal effects in the gastrointestinal tract. Recent observation by our group that this classical gastrointestinal hormone is readily releasable from hypothalamic neurons upon K+-evoked depolarization suggested a potential influence of this peptide on the neuronal activity within this brain region. We hereby showed that intracerebroventricularly-injected secretin could elevate c-fos and vasopressin (VP) gene expression in the magnocellular subdivision of the Paraventricular Nucleus as well as throughout the Supraoptic Nucleus. In addition, it could also enhance, through a cAMP/PKA-dependent pathway, the basal release of VP from the hypothalamic explants. Together with the fact that secretin is expressed at high concentrations in the circumventricular subfornical organ, which contains osmoreceptor cells that regulate the plasma osmolality, as well as its releasing ability from the somatodendritic and axonal compartments of the magnocellular neurons via a TTX-sensitive and Ca2+-dependent mechanism, it is speculated that locally released secretin in the hypothalamo– neurohypophysial system could act in autocrine and/or paracrine manners via its G protein-coupled receptor to modulate osmoregulation.