title: Adrenomedullin 2 (AM2)/intermedin is a more potent activator of hypothalamic oxytocin-secreting neurons than AM possibly through an unidentified receptor in rats.
abstract: Central administration of either adrenomedullin 2 (AM2) or adrenomedullin (AM) activates hypothalamic oxytocin (OXT)-secreting neurons in rats. We compared AM2 with AM, given intracerebroventricularly (icv), across multiple measures: (1) plasma OXT levels in conscious rats; (2) blood pressure, heart rate and circulating catecholamine levels in urethane-anesthetized rats; and (3) the expression of the c-fos gene in the supraoptic (SON) and the paraventricular nuclei (PVN). We also tested the effects of the AM receptor antagonist, AM(22-52) and calcitonin gene-related peptide (CGRP) antagonist, CGRP(8-37) on these measures. Plasma OXT levels at 10 min after icv injection of AM (1 nmol/rat) were increased (compared with vehicle), but OXT levels after AM2 (1 nmol/rat) were nearly double the levels seen after AM injection. OXT levels remained elevated at 30 min. Pretreatment with AM(22-52) (27 nmol/rat) and CGRP(8-37) (3 nmol/rat), nearly abolished the increase in plasma OXT level after AM injection, but partially blocked OXT level changes due to AM2. Increases in blood pressure, heart rate and circulating catecholamines were all greater in response to central AM2 than to AM at the same dose. In situ hybridization histochemistry showed that both AM2 and AM induced expression of the c-fos gene in the SON and the PVN, but AM(22-52)+CGRP(8-37) could only nearly abolish the effects of centrally administered AM. These results suggest that the more potent central effects of AM2 and only partial blockade by AM/CGRP receptor antagonists may result from its action on an additional, as yet unidentified, specific receptor in the central nervous system.
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Hirofumi
authors: H
authors: Hashimoto
authors: Susumu
authors: S
authors: Hyodo
authors: Makoto
authors: M
authors: Kawasaki
authors: Minori
authors: M
authors: Shibata
authors: Takeshi
authors: T
authors: Saito
authors: Hitoshi
authors: H
authors: Suzuki
authors: Hiroki
authors: H
authors: Otsubo
authors: Toru
authors: T
authors: Yokoyama
authors: Hiroaki
authors: H
authors: Fujihara
authors: Takashi
authors: T
authors: Higuchi
authors: Yoshio
authors: Y
authors: Takei
authors: Yoichi
authors: Y
authors: Ueta
mesh_terms: D053607:Adrenomedullin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D010121:Oxytocin; D015740:Calcitonin Gene-Related Peptide