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Am J Physiol Endocrinol Metab (June 14, 2005). doi:10.1152/ajpendo.00042.2005
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Submitted on February 4, 2005
Accepted on June 9, 2005

Centrally Administered Adrenomedullin 2 Activates Hypothalamic Oxytocin-Secreting Neurons Causing Elevated Plasma Oxytocin Level in Rats

Hirofumi Hashimoto1, Susumu Hyodo2, Makoto Kawasaki1, Takashi Mera1, Lei Chen1, Atsushi Soya1, Takeshi Saito1, Hiroaki Fujihara1, Takashi Higuchi3, Yoshio Takei2, and Yoichi Ueta1*

1 Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
2 Laboratory of Physiology, Department of Marine Bioscience, Ocean Research Institute, University of Tokyo, Tokyo, Japan
3 Department of Integrative Physiology, University of Fukui, Fukui, Japan

* To whom correspondence should be addressed. E-mail: yoichi{at}med.uoeh-u.ac.jp.

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) in comparison 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 5-180 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 in comparison 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 CGRP antagonist, CGRP8-37 (3 nmol/rat) and the AM receptor antagonist, AM22-52 (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.




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[Abstract] [Full Text] [PDF]


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