Novel fish-derived adrenomedullin in mammals: structure and possible function

Takei, Yoshiyuki; Hyodo, Susumu; Katafuchi, Tetsuro; Minamino, Naoto

doi:10.1016/j.peptides.2004.06.026

Cited by 90 publications

(76 citation statements)

References 82 publications

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“…It can be considered that AM5 elicited its effects through AM and/or AM2 receptors. AM5, as well as AM and AM2, has a characteristic structure that includes an intramolecular ring structure of six amino acid residues flanked by a single disulfide bond and amidated carboxyl ends (Takei et al 2004b, Ogoshi et al 2006. In the present study, the effects of centrally administered AM5 on plasma OXT levels were similar to the effects of AM and AM2 (Serino et al 1999, Hashimoto et al 2005.…”

Section: Discussionsupporting

confidence: 72%

Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

Otsubo¹,

Hyodo²,

Hashimoto³

et al. 2009

Journal of Endocrinology

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We examined the effects of i.c.v. administration of adrenomedullin 5 (AM5) on the brain of conscious rats. We used porcine AM5 in the present study because rat AM5 has not been detected. We observed Fos-like immunoreactivity (LI) in the hypothalamus and brainstem of conscious rats after i.c.v. administration of AM5 (2 nmol/rat). Fos-LI, measured at 90 min post-AM5 injection, was observed in various brain areas, including the supraoptic (SON) and the paraventricular nuclei (PVN). Dual immunostaining for Fos/oxytocin (OXT) and Fos/arginine vasopressin (AVP) revealed that OXT-LI neurones predominantly colocalized Fos-LI compared with AVP-LI neurones in the SON and the PVN. Plasma OXT levels were significantly increased 5 min after i.c.v. administration of AM5 (1 nmol/rat) compared with vehicle and remained elevated in samples taken at 15 and 30 min without changes in plasma AVP levels at any time. In situ hybridization histochemistry showed that i.c.v. administration of AM5 (0 . 2, 1 and 2 nmol/rat) caused a marked induction of the expression of the c-fos gene in the SON and the PVN. This induction was significantly but not completely 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). Although porcine AM5 has not been detected yet in the brain, these results suggest that centrally administered porcine AM5 may activate OXT-secreting neurosecretory cells in the hypothalamus partly through AM/CGRP receptors and elicit secretion of OXT into the systemic circulation in conscious rats.

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Section: Discussionsupporting

confidence: 72%

Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

Otsubo¹,

Hyodo²,

Hashimoto³

et al. 2009

Journal of Endocrinology

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“…It appeared that IMD's cardio-protective effect was achieved through modulating the expression of apoptosis-related factors. It was generally thought that the cardiovascular protective effect of IMD is derived from its vasodilating function, which attenuates vasoconstriction and ischemic damage [11,13,24,25]. In addition, it has been shown that deprivation of oxygen and ischemic reperfusion resulted in apoptosis of cardiomyocytes [23,26].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of intermedin on myocardial cell in a rat model of severe acute pancreatitis

Cao

Xue

et al. 2011

Cellular and Molecular Biology Letters

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Abstract:Severe acute pancreatitis (SAP) is a common disease with a poor prognosis. Heart failure is one cause of SAP patient death. Intermedin (IMD) is a potent endogenous cardio-protective substance. Administration of exogenous IMD showed beneficial effects in cardiovascular diseases. The aim of this study was to investigate the myocardial damage in SAP and to determine the therapeutic potential of IMD for SAP. Using an SAP rat model, we examined endogenous IMD expression following SAP induction, and determined the effect of IMD on myocardial function, histological morphology, apoptosis-related gene expression, and prognosis. Our results indicated that the cardiac function and histological structure were significantly disrupted in SAP rats. Infusion of exogenous IMD significantly preserved cardiac function and ameliorated myocardial damage. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) revealed that myocardial apoptosis was extensively present in SAP rats, and IMD infusion led to increased expression of the prosurvival factor Bcl-2, but decreased pro-apoptotic factors Bax and caspase-3. In addition, IMD infusion also reversed the change of IMD receptor systems in SAP rat heart tissue. Furthermore, we found that IMD infusion greatly decreased mortality of SAP rats. In conclusion, administration of SAP produced therapeutic effects in SAP through modulating apoptotic and pro-survival gene expression, inhibiting myocardial apoptosis, preserving cardiac function, and ultimately increasing survival. The current study suggests that IMD may be a useful therapeutic agent for SAP, and provides us an insight for a clinical trial of IMD for treating human severe acute pancreatitis.

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“…Judging from the high affinity of CGRP, AM, and amylin to CTR/CLR coupled with one of RAMPs (10 K11 -10 K9 M), which is in a range of endogenous variation of plasma concentrations, these peptides may act also as an endocrine hormone from plasma (Eto et al 2003). However, the potency of AM2 for cAMP accumulation in CLR-RAMP was much lower than AM (Roh et al 2004, Takei et al 2004a, while its central actions are even greater than AM (Hashimoto et al 2007). In addition, the AM2 effect was blocked only partially by CGRP 8-37 and AM , although the AM effect was totally blocked by combination of the two blockers.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of the AM gene is enhanced in various forms of cardiac failure and renal dysfunction, causing protective actions on the heart and kidney (Tsuruda & Burnett 2002). The AM2 gene is expressed in the brain and kidney of mammals and exerts various central and peripheral actions on cardiovascular and body fluid regulation (Roh et al 2004, Takei et al 2004a, Taylor et al 2005, Yang et al 2005, Takahashi et al 2006. Amylin, a pancreatic hormone that is secreted with insulin from b cells (Cluck et al 2005), exhibits a weak vasorelaxant effect (1/100 of CGRP).…”

Section: Introductionmentioning

confidence: 99%

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

Takei¹,

Hashimoto

Inoue³

et al. 2008

Journal of Endocrinology

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Adrenomedullin 5 (AM5) is a new member of the calcitonin gene-related peptide (CGRP) family identified in teleost fish. Although its presence was suggested in the genome database of mammals, molecular identity and biological function of AM5 have not been examined yet. In this study, we cloned a cDNA encoding AM5 in the pig and examined its cardiovascular and renal effects. Putative mature AM5 was localized in the middle of prohormone and had potential signals for intermolecular ring formation and C-terminal amidation. The AM5 gene was expressed most abundantly in the spleen and thymus. Several AM5 genes were newly identified in the database of mammals, which revealed that the AM5 gene exists in primates, carnivores, and undulates but could not be identified in rodents. In primates, nucleotide deletion occurred in the mature AM5 sequence in anthropoids (human and chimp) during transition from the rhesus monkey. Synthetic mature AM5 injected intravenously into rats induced dose-dependent decreases in arterial pressure at 0 . 1-1 nmol/kg without apparent changes in heart rate. The decrease was maximal in 1 min and AM5 was approximately half as potent as AM. AM5 did not cause significant changes in urine flow and urine Na C concentration at any dose. In contrast to the peripheral vasodepressor action, AM5 injected into the cerebral ventricle dose-dependently increased arterial pressure and heart rate at 0 . 1-1 nmol. The increase reached maximum more quickly after AM5 (5 min) than AM (15-20 min). AM5 added to the culture cells expressing calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) together with one of the receptor activitymodifying proteins (RAMPs), the combination of which forms major receptors for the CGRP family, did not induce appreciable increases in cAMP production in any combination, although AM increased it at 10 K10 -10 K9 M when added to the CLR and RAMP2/3 combination. These data indicate that AM5 seems to act on as yet unknown receptor(s) for AM5, other than CLR/CTRCRAMP, to exert central and peripheral cardiovascular actions in mammals.

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Novel fish-derived adrenomedullin in mammals: structure and possible function

Cited by 90 publications

References 82 publications

Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

Protective effect of intermedin on myocardial cell in a rat model of severe acute pancreatitis

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

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