Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei

Agmatine (decarboxylated L-arginine), an endogenous ligand of imidazoline a nd alpha (2) adrenoreceptors, is particularly enriched in the rat hypothala mic paraventricular (PVN) and supraoptic (SON) nuclei. The present study ut ilized light and electron microscopic immunocytochemical methods to determi ne the distribution and extent of colocalization. of agmatine relative to s ubpopulations of vasopressin- (VP) and oxytocin- (OT) producing neurons in PVN and SON nuclei. By light microscopy, agmatine-immunoreactive perikarya were found in both the magnocellular and the parvocellular neuronal subdivi sions of PVN and SON. Confocal and electron microscopy revealed that agmati ne-immunoreactivity M within neuronal perikarya was associated with the nuc lear membrane as well as mitochondria, Golgi complexes, endoplasmic reticul a, and plasmalemma. Additionally, agmatine-I was identified in both axons a nd axonal terminals, which were enriched in large dense-core vesicles. Dual and triple immunocytochemical labeling experiments also demonstrated that agmatine coexists with VP or OT in most PVN and SON magnocellular neurons. Combinations of iontophoretic injections of Fluorogold into the dorsomedull ary complex with immunocytochemical labeling revealed that many retrogradel y labeled neurons in the parvocellular region of the PVN contained agmatine -1 and either VP or OT. These findings provide evidence that agmatine may f unction as a modulator of both hypothalamically mediated neuroendocrine and autonomic responses. (C) 2001 Academic Press.