Centrally administered adrenomedullin 2 activates hypothalamic oxytocin-secreting neurons, causing elevated plasma oxytocin level in rats

• Published in: American journal of physiology: endocrinology and metabolism 2005-11, Vol.289 (5), p.E753-E761
• Main Authors: Hashimoto, Hirofumi, Hyodo, Susumu, Kawasaki, Makoto, Mera, Takashi, Chen, Lei, Soya, Atsushi, Saito, Takeshi, Fujihara, Hiroaki, Higuchi, Takashi, Takei, Yoshio, Ueta, Yoichi
• Format: Article
• Language: English
• Subjects: Adrenomedullin; Animals; Arginine Vasopressin - antagonists & inhibitors; Arginine Vasopressin - blood; Arginine Vasopressin - metabolism; Calcitonin Gene-Related Peptide - pharmacology; Calcitonin Gene-Related Peptide Receptor Antagonists; Immunohistochemistry; In Situ Hybridization; Injections, Intraventricular; Male; Neurons - drug effects; Neurons - metabolism; Neuropeptides - pharmacology; Oxytocin - antagonists & inhibitors; Oxytocin - blood; Oxytocin - metabolism; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Peptide Fragments - pharmacology; Proto-Oncogene Proteins c-fos - biosynthesis; Proto-Oncogene Proteins c-fos - genetics; Rats; Rats, Wistar; Supraoptic Nucleus - cytology; Supraoptic Nucleus - drug effects; Supraoptic Nucleus - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00042.2005

1 Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu; 2 Laboratory of Physiology, Department of Marine Bioscience, Ocean Research Institute, University of Tokyo, Tokyo; and 3 Department of Integrative Physiology, University of Fukui, Fukui, Japan Submitted 4 February 2005 ; accepted in final form 9 June 2005 We examined the effects of intracerebroventricular (ICV) administration of adrenomedullin 2 (AM2) on plasma oxytocin (OXT) and arginine vasopressin (AVP) levels in conscious rats. Plasma OXT levels were markedly increased 5 min after ICV administration of AM2 (1 nmol/rat) compared with vehicle and remained elevated in samples taken at 10, 15, 30, and 60 min. By contrast, plasma AVP levels were not significantly elevated in samples taken between 5 and 180 min after ICV administration of AM2 except at the 30-min time point. Fos-like immunoreactivity (Fos-LI) was observed in various brain areas, including the paraventricular (PVN) and the supraoptic nuclei (SON) after ICV administration of AM2 (2 nmol/rat) in conscious rats (measured at 90 min post-AM2 infusion). Dual immunostaining for OXT/Fos and AVP/Fos showed that OXT-LI neurons predominantly exhibited nuclear Fos-LI compared with AVP-LI neurons in the PVN and the SON. In situ hybridization histochemistry showed that ICV administration of AM2 (0.2, 1, and 2 nmol/rat) caused marked induction of the expression of the c- fos gene in the PVN and the SON. This induction was significantly reduced by pretreatment with both the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8–37) (3 nmol/rat) and the AM receptor antagonist AM-(22–52) (27 nmol/rat). These results suggest that centrally administered AM2 mainly activates OXT-secreting neurons in the PVN and the SON, at least in part through the CGRP and/or AM receptors with marked elevation of plasma OXT levels in conscious rats. c- fos ; fos; paraventricular nucleus; supraoptic nucleus; vasopressin Address for reprint requests and other correspondence: Y. Ueta, Dept. of Physiology, School of Medicine, Univ. of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan (e-mail: yoichi{at}med.uoeh-u.ac.jp )