Neuroendocrine regulatory peptide-1 and -2 (NERPs) inhibit the excitability of magnocellular neurosecretory cells in the hypothalamus.
Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 (NERPs) are novel carboxy-terminally amidated peptides derived from the neurosecretory protein VGF. NERPs are colocalized with vasopressin in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus, and suppress vasopressin secretion evoked by intracerebroventricular administration of angiotensin II (AngII) and hypertonic saline or bath administration of AngII. Magnocellular neurosecretory cells (MCNs) of the hypothalamus release vasopressin and oxytocin from their dendrites and soma. The two cell types have common electrophysiological properties in response to glutamate and AngII. We investigated the mechanisms underlying the suppressive effects of NERPs on MCNs. Microdialysis of the PVN demonstrated that NERPs suppressed glutamate release induced by AngII. A whole-cell patch-clamp study of the SON showed that NERPs suppressed the potentiation of excitatory postsynaptic currents (EPSCs) evoked by AngII without affecting the amplitude, indicating that NERPs suppressed EPSCs by a presynaptic mechanism. The suppressive effect of NERP-2, but not NERP-1, was blunted in the presence of tetrodotoxin and bicuculline, a γ-aminobutyric acid (GABA) A receptor antagonist. These results indicate that NERP-1 suppresses presynaptic glutamatergic neurons connected to MNCs, whereas NERP-2 activates GABAergic interneurons, which suppress presynaptic glutamatergic neurons; thus, both peptides suppress vasopressin release. This study demonstrates that NERPs function as inhibitory modulators of vasopressin release.
Department of Neurology, Respirology, Endocrinology and Metabolism, Faculty of Internal Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Koji
K
Toshinai
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
Takeshi
T
Saito
Department of Neurology, Respirology, Endocrinology and Metabolism, Faculty of Internal Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Hideki
H
Yamaguchi
Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan.
Kazuki
K
Sasaki
Department of Neurology, Respirology, Endocrinology and Metabolism, Faculty of Internal Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Wakaba
W
Tsuchimochi
Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan.
Naoto
N
Minamino
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
Yoichi
Y
Ueta
Department of Neurology, Respirology, Endocrinology and Metabolism, Faculty of Internal Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan. Electronic address: nakazato@med.miyazaki-u.ac.jp.
Masamitsu
M
Nakazato
D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D009419:Nerve Tissue Proteins; C523894:neuroendocrine regulatory peptide-1, rat; C523896:neuroendocrine regulatory peptide-2, rat; D018698:Glutamic Acid
EPSCs; PVN; Presynaptic mechanism; SON; VGF-derived peptides