Centrally administered adrenomedullin 2 activates hypothalamic oxytocin-secreting neurons, causing elevated plasma oxytocin level in rats.
We examined the effects of intracerebroventricular (i.c.v.) 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 i.c.v. 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 i.c.v. 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 i.c.v. 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 i.c.v. 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.
Hashimoto
Hirofumi
H
Dept. of Physiology, School of Medicine, Univ. of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Hyodo
Susumu
S
Kawasaki
Makoto
M
Mera
Takashi
T
Chen
Lei
L
Soya
Atsushi
A
Saito
Takeshi
T
Fujihara
Hiroaki
H
Higuchi
Takashi
T
Takei
Yoshio
Y
Ueta
Yoichi
Y
D053607:Adrenomedullin; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C499411:Adm2 protein, rat; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D009479:Neuropeptides; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; C104782:adrenomedullin (22-52); D001127:Arginine Vasopressin; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D010121:Oxytocin; D015740:Calcitonin Gene-Related Peptide