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A physiological role for adrenomedullin in rats; a potent hypotensive peptide in the hypothalamo‐neurohypophysial system
Author(s) -
Ueta Yoichi,
Serino Ryota,
Shibuya Izumi,
Kitamura Kazuo,
Kangawa Kenji,
Russell John A.,
Yamashita Hiroshi
Publication year - 2000
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1111/j.1469-445x.2000.tb00020.x
Subject(s) - adrenomedullin , supraoptic nucleus , medicine , endocrinology , hypothalamus , oxytocin , vasopressin , neuropeptide , nucleus , chemistry , biology , receptor , microbiology and biotechnology
Adrenomedullin, a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Adrenomedullin immunoreactivity and gene expression are found not only in peripheral organs but also in the central nervous system. Adrenomedullin labelled cells were localised in the hypothalamus, including in the paraventricular and supraoptic nuclei, in rats. Abundant adrenomedullin‐immunoreactive fibres and varicosities were found in the hypothalamo‐neurohypophysial tract and the internal zone of the median eminence in colchicine‐treated and hypophysectomized rats, whereas in control rats few adrenomedullin‐labelled fibres were observed. We examined the effects of intracerebroventricular administration of adrenomedullin on neurosecretory cells in the paraventricular and supraoptic nuclei of rats, using immuno‐histochemistry for Fos protein and in situ hybridisation histochemistry for c‐fos mRNA. Intracerebroventricular administration of adrenomedullin caused a marked induction of Fos‐like immunoreactivity in the paraventricular nucleus and the dorsal part of the supraoptic nucleus. In the paraventricular and supraoptic nuclei, nuclear Fos‐like immunoreactivity was predominantly in oxytocin‐immunoreactive cells rather than vasopressin‐immunoreactive cells. The induction of c‐fos mRNA in the paraventricular and supraoptic nuclei was increased in a dose‐related manner 30 min after intracerebroventricular administration of adrenomedullin. This induction was reduced by pre‐treatment with the adrenomedullin receptor antagonist, human adrenomedullin‐(22–52)‐NH 2 Intracerebroventricular administration of adrenomedullin also caused a marked increase in the plasma concentration of oxytocin. Extracellular recordings from magnocellular neurosecretory cells in the paraventricular nucleus revealed that putative oxytocin‐secreting cells were activated by intracerebroventricular administration of adrenomedullin. These results suggest that central adrenomedullin preferentially stimulates the secretion of oxytocin by activating hypothalamic oxytocin‐secreting cells and may have an important role in salt appetite and body fluid homeostasis in rats.