Distribution of preproadrenomedullin mRNA in the rat central nervous system and its modulation by physiological stressors

Shan, Jing; Krukoff, Teresa L.

doi:10.1002/cne.1090

Cited by 54 publications

(37 citation statements)

References 66 publications

(62 reference statements)

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“…ADM and its receptor have been shown to be expressed in the central nervous system (CNS) and its cellular components [10,28,29]. The direct effects of ADM on sympathetic nerve activity in conscious rats have been observed and these studies are consistant with the observations reported by Takekoshi and colleagues [30], who showed that in anesthetized rats, icv ADM induces an increase in preganglionic sympathetic discharge.…”

mentioning

confidence: 75%

The Effect of Adrenomedullin (ADM) on Tyrosine Hydroxylase (TH) Enzyme Activity and Blood Pressure in Cold Exposed Rats

Yüksel

Yürekli

2003

Endocr J

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Abstract. It is known that, under stress conditions the hypothalamo-pituitary-adrenal (HPA) axis is stimulated and catecholamine production is increased. Adrenomedullin (ADM) is a novel peptide that elicits a long-vasorelaxation, and participates in blood pressure regulation via different mechanisms. In the present study, we investigated the administration of ADM on tyrosine hydroxylase (TH) enzyme activity in cold exposed rats. Four groups of SpragueDawley rats were studied for their TH enzyme activity in the adrenal medulla and hypothalamus. In addition to measuring blood pressure in these rats, TH enzyme activity in both the adrenal medulla and hypothalamus were examined in four groups of Sprague-Dawley rats: animals exposed to room temperature and cold stress (8ºC, 48 h), and rats injected with ADM (1.0 nmol/kg, i.v.) alone and/or together with cold stress. TH activity was shown to be increased in cold treated groups and decreased in ADM and ADM + cold stress group. Our findings appear to suggest that external ADM application caused an opposite effect on the same system in rats, decreasing the activity of tyrosine hydroxylase (TH) enzyme activity. Furthermore, externally applied ADM was shown to produce its expected hypotensive effect in coldstressed rats. Our results suggest that a possible explanation for the effects of ADM is that, the uptake of ADM under cold stress may effect TH activity in studied tissues.

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confidence: 75%

The Effect of Adrenomedullin (ADM) on Tyrosine Hydroxylase (TH) Enzyme Activity and Blood Pressure in Cold Exposed Rats

Yüksel

Yürekli

2003

Endocr J

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“…In a similar way, s.c. injection of PAMP provoked an elevation on ACTH and corticosterone in the rat (31). In addition, several articles demonstrate that when humans or experimental animals are subjected to a diverse battery of stressors (restraint, dehydration, cold, disease, acute exercise, or psychological pressure) the common response is a sharp elevation on the levels of tissue and circulating AM (32)(33)(34). In our mice lacking adm in the brain, we observed a behavior consistent with higher basal stress levels when compared to their wild-type littermates.…”

Section: Discussionmentioning

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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“…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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Distribution of preproadrenomedullin mRNA in the rat central nervous system and its modulation by physiological stressors

Cited by 54 publications

References 66 publications

The Effect of Adrenomedullin (ADM) on Tyrosine Hydroxylase (TH) Enzyme Activity and Blood Pressure in Cold Exposed Rats

The Effect of Adrenomedullin (ADM) on Tyrosine Hydroxylase (TH) Enzyme Activity and Blood Pressure in Cold Exposed Rats

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

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

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