Distribution of adrenomedullin-like immunoreactivity in the rat central nervous system by light and electron microscopy

Serrano, Julia; Uttenthal, L. O.; Martı́nez, Alfredo; Fernández, Ana Patricia; Velasco, Javier Martı́nez de; Alonso, David; Bentura, M. L.; Santacana, Marı́a; Gallardo, José R; Martı́nez-Murillo, Ricardo; Cuttitta, Frank; Rodrigo, José

doi:10.1016/s0006-8993(99)02273-8

Cited by 100 publications

(75 citation statements)

References 60 publications

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“…AM is a 52 aa peptide and is broadly distributed in the CNS (Serrano et al, 2000;Shan and Krukoff, 2001). This peptide belongs to a family that includes AM2 (intermedin) (Roh et al, 2004), CGRP, amylin (Poyner et al, 2002), and calcitonin receptor-activating peptides (Katafuchi et al, 2003a,b).…”

Section: Introductionmentioning

confidence: 99%

A Role for Protein Kinase C-Dependent Upregulation of Adrenomedullin in the Development of Morphine Tolerance in Male Rats

Yu¹,

Wang²,

Chabot³

et al. 2010

J. Neurosci.

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Section: Introductionmentioning

confidence: 99%

A Role for Protein Kinase C-Dependent Upregulation of Adrenomedullin in the Development of Morphine Tolerance in Male Rats

Yu¹,

Wang²,

Chabot³

et al. 2010

J. Neurosci.

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“…AM expression is upregulated under hypoxic conditions through hypoxia-inducible factor-1 (HIF-1) (Garayoa et al 2000) and has been found in many structures of the central nervous system (Serrano et al 2000). In addition, exposure of the rat brain to ischemia reperfusion results in a dramatic increase in AM expression in both neural and vascular structures of the brain (Serrano et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin expression and function in the rat carotid body

Martı́nez¹,

Saldise²,

Ramı́rez³

et al. 2003

Journal of Endocrinology

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Adrenomedullin (AM) immunoreactivity has been found in granules of the glomus (type I) cells of the carotid bodies in rats. The identity of these cells was ascertained by colocalization of immunoreactivities for AM and tyrosine hydroxylase in their cytoplasm. Exposure of freshly isolated carotid bodies to synthetic AM resulted in a concentration-and time-dependent degranulation of glomus cells as measured by dopamine (DA) release. DA release reached a zenith 30 min after exposure to AM (94·2% over untreated controls). At this time-point, the response to AM was similar to the one elicited by 5 min of exposure to 100 mM K + . Nevertheless, injection of 1 µl 60 nM AM/g body weight into the tail vein of the rats did not induce statistical differences in DA release from the carotid bodies. Exposure of the oxygen-sensitive cell line PC-12 to hypoxia elicited an increase in AM mRNA expression and peptide secretion into serum-free conditioned medium. Previous data have shown that elevation of AM expression under hypoxia is mediated through hypoxia-inducible factor-1, and that exposure of chromaffin cells to AM results in degranulation. All these data suggest that AM is an important autocrine regulator of carotid body function.

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“…In the CNS, AM was initially found in the hypothalamus (3), but later on it became clear that this peptide is expressed throughout the whole brain (4). Components of the AM receptor system are also found in most areas of the brain (5), providing an anatomical basis for the implication of AM in brain physiology.…”

mentioning

confidence: 99%

Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions

Fernández

Serrano²,

Tessarollo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous system (CNS) and several functions have been suggested for brain AM. Until now, a formal confirmation of these actions using genetic models has been elusive since the systemic adm knockout results in embryo lethality. We have built a conditional knockout mouse model using the Cre/loxP approach. When crossed with transgenic mice expressing the Cre recombinase under the tubulin T␣-1 promoter, we obtained animals with no AM expression in the CNS but normal levels in other organs. These animals lead normal lives and do not present any gross morphological defect. Specific areas of the brain of animals lacking CNS AM contain hyperpolymerized tubulin, a consequence of AM downregulation. Behavioral analysis shows that mice with no AM in their brain have impaired motor coordination and are hyperactive and overanxious when compared to their wild-type littermates. Treatment with methylphenidate, haloperidol, and diazepam did not show differences between genotypes. Circulating levels of adrenocorticotropic hormone and corticosterone were similar in knockout and wild-type mice. Animals with no brain AM were less resistant to hypobaric hypoxia than wild-type mice, demonstrating the neuroprotective function of AM in the CNS. In conclusion, AM exerts a beneficial action in the brain by maintaining homeostasis both under normal and stress conditions. A drenomedullin (AM) is a 52-aa regulatory peptide with structural homology to calcitonin gene-related peptide (CGRP) and amylin. The adm gene is located in mouse chromosome 7 and codes for a preprohormone which, after posttranslational modifications, generates 2 biologically active peptides, AM and proadrenomedullin N-terminal 20 peptide (PAMP). Expression of these peptides is widespread and several functions have been ascribed to these molecules, including vasodilatation, bronchodilatation, hormone secretion regulation, growth modulation, angiogenesis promotion, and antimicrobial activity, among others (1). The receptor system for AM consists of a heterodimer composed of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP) type 2 or 3 (2).In the CNS, AM was initially found in the hypothalamus (3), but later on it became clear that this peptide is expressed throughout the whole brain (4). Components of the AM receptor system are also found in most areas of the brain (5), providing an anatomical basis for the implication of AM in brain physiology. Receptor autoradiography studies have shown that AM is able to bind to many areas of the brain, as well (6). Recently, a new member of the CGRP/AM peptide family, with a peptide sequence similar to AM but coded by a different gene, has been reported and named AM2 or intermedin. This peptide has similar actions and distribution in the brain to original AM (7).Several observations suggest that AM could act as a neurotransmitter or neuromodulator. For instance, direct injection of AM in the CNS induces vasoconstriction (8), an incre...

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Distribution of adrenomedullin-like immunoreactivity in the rat central nervous system by light and electron microscopy

Cited by 100 publications

References 60 publications

A Role for Protein Kinase C-Dependent Upregulation of Adrenomedullin in the Development of Morphine Tolerance in Male Rats

A Role for Protein Kinase C-Dependent Upregulation of Adrenomedullin in the Development of Morphine Tolerance in Male Rats

Adrenomedullin expression and function in the rat carotid body

Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions

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