Adrenomedullin influences magnocellular and parvocellular  neurons of paraventricular nucleus via separate mechanisms

Follwell, Matthew; Ferguson, Alastair V.

doi:10.1152/ajpregu.00191.2002

Cited by 13 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data from HNS explants (Fig. 2) and single-cell recordings from magnocellular PVN neurons (6) indicate that the stimulatory effects of AM on AVP secretion are exerted indirectly through interneurons, suggesting that transcriptional control of AVP by AM may also be through indirect actions.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived adrenomedullin controls blood volume through the regulation of arginine vasopressin production and release

Taylor¹,

Baker²,

Samson³

2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

tral nervous system-derived adrenomedullin (AM) has been shown to be a physiological regulator of thirst. Administration of AM into the lateral ventricle of the brain attenuated water intake, whereas a decrease in endogenous AM, induced by an AM-specific ribozyme, led to exaggerated water intake. We hypothesized that central AM may control fluid homeostasis, in part by regulating plasma arginine vasopressin (AVP) levels. To test this hypothesis, AM or a ribozyme specific to AM was administered intracerebroventricularly, and alterations in plasma AVP concentrations were examined under basal and stimulated (hypovolemic) conditions. Additionally, we examined changes in blood volume, kidney function, and plasma electrolyte and protein levels, as well as changes in plasma aldosterone concentrations. Intracerebroventricular administration of AM increased plasma AVP levels, whereas AM ribozyme treatment led to decreased plasma AVP levels under stimulated conditions. During hypovolemic challenges, AM ribozyme treatment led to an increased loss of plasma volume compared with control animals. Although overall plasma osmolality did not differ between treatment groups during hypovolemia, aldosterone levels were significantly higher and, consequently, plasma potassium concentrations were lower in AM ribozyme-treated rats than in controls. These data suggest that brain-derived AM is a physiological regulator of vasopressin secretion and, thereby, fluid homeostasis.ribozyme; proadrenomedullin amino-terminal 20 peptide; aldosterone POSTTRANSLATIONAL PROCESSING of the adrenomedullin (AM) gene product results in two biologically active proteins, proadrenomedullin NH 2 -terminal 20 peptide (PAMP) and AM. AM, a member of the calcitonin peptide family, is a vasoactive peptide that is produced in many peripheral tissues as well as in the central nervous system. The AM receptor calcitonin receptor-like receptor, in association with receptor activitymodifying protein 2 or 3 (1, 17), is also present in the central nervous system (23, 33) and is particularly abundant in the hypothalamus (41). Additionally, there are several reports that intracerebroventricular administration of AM increased c-fos mRNA and Fos protein in many areas of the hypothalamus, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON) (32, 42). The PVN and SON contain neuronal cell bodies that produce arginine vasopressin (AVP) and/or oxytocin (OT) and project to the neural lobe of the pituitary.There is a great deal of evidence suggesting that central and peripheral AM regulates fluid and electrolyte balance. Centrally, AM has been proven to be a physiological regulator of thirst and sodium appetite. Central AM administration decreased water intake to a variety of classical drinking paradigms (19), whereas decreased endogenous AM (by an AMspecific ribozyme) (40) led to exaggerated water intake under these same paradigms. Similarly, central administration of AM decreased salt appetite (31), whereas compromise of central AM (through passive immunoneu...

show abstract

Section: Discussionmentioning

confidence: 99%

Brain-derived adrenomedullin controls blood volume through the regulation of arginine vasopressin production and release

Taylor¹,

Baker²,

Samson³

2005

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…In addition, these observations suggested important roles for GABA interneurons, the majority of which are localized in the halo zone surrounding the PVN [10], as an additional gatekeeper/integrator in controlling the excitability of PVN outputs. Important roles for these GABA interneurons have now been suggested in mediating inhibitory effects of adrenomedullin [52] on magnocellular, excitatory effects (presumably through disinhibition) of ANG on preautonomic [53], and IL-1β [37] on parvocellular neurons.…”

Section: Roles For Interneurons In the Regulation Of Pvn Output Neuronsmentioning

confidence: 99%

The paraventricular nucleus of the hypothalamus – a potential target for integrative treatment of autonomic dysfunction

Ferguson

Latchford

Samson

2008

Expert Opinion on Therapeutic Targets

266

178

View full text Add to dashboard Cite

Background-The paraventricular nucleus of the hypothalamus (PVN) has emerged as one of the most important autonomic control centers in the brain, with neurons playing essential roles in controlling stress, metabolism, growth, reproduction, immune, and other more traditional autonomic functions (gastrointestinal, renal and cardiovascular).Objectives-Traditionally the PVN was viewed very much as a nucleus in which afferent inputs from other regions were faithfully translated into changes in single specific outputs whether those were neuroendocrine or autonomic. Here we will present data which suggest that PVN in fact plays significant and essential roles in integrating multiple sources of afferent input and sculpting an integrated autonomic output by concurrently modifying the excitability of multiple output pathways. In addition we will highlight recent work which suggests that dysfunction of such intranuclear integrative circuitry may contribute to the pathology of conditions such as hypertension and congestive heart failure.Conclusions-This review highlights data showing that individual afferent inputs (SFO), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways. We also highlight recent studies showing that modifications in this integrated circuitry may play significant roles in the pathology of diseases such as congestive heart failure and hypertension.

show abstract

“…These data suggest that NO in the PVN is one of the candidates to mediate the ADM-induced decrease in arterial pressure. In addition, GABA exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the PVN [31,32], and a selective GABA A receptor antagonist, bicuculline, abolishes ADM-induced hyperpolarization of magnocellular neurons in the PVN [33], suggesting that GABA may also contribute to the hypotensive effect of ADM within the PVN.…”

Section: Introductionmentioning

confidence: 99%

Decrease in arterial pressure induced by adrenomedullin in the hypothalamic paraventricular nucleus is mediated by nitric oxide and GABA

Krukoff

2004

Regulatory Peptides

View full text Add to dashboard Cite

We tested the hypothesis that the decrease in arterial pressure induced by adrenomedullin (ADM) in the hypothalamic paraventricular nucleus (PVN) is mediated by nitric oxide (NO) and/or GABA. Unilateral microinjections of ADM into the PVN of anesthetized rats caused a significant decrease in mean arterial pressure (MAP). The ADM-induced decrease in MAP was significantly attenuated by pretreatment with N ψ -nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor), 7-nitroindazole sodium salt (7-NiNa, a selective neuronal NOS inhibitor), N5-(1-Iminoethyl)-L-ornithine (L-NIO, a selective endothelial NOS inhibitor) or bicuculline methiodide, but pretreatment with S-methylisothiourea (SMIT, a selective inducible NOS inhibitor) had no effect on this ADM-induced effect. In addition, coronal sections of rat brains were processed for combined NADPH-diaphorase (a marker of neuronal NOS-containing neurons) histochemistry and in situ hybridization for the receptor-activity-modifying protein 2 (a specific ADM receptor component). Double-labeled neurons were found in both parvocellular and magnocellular subdivisions of the PVN, confirming that NO-producing neurons in the PVN are capable of mediating ADM's effects. Thus, our data provide evidence that the ADM-induced decrease in MAP in the PVN is mediated by NO from neuronal and endothelial NOS, and by GABA.

show abstract

Adrenomedullin influences magnocellular and parvocellular neurons of paraventricular nucleus via separate mechanisms

Cited by 13 publications

References 37 publications

Brain-derived adrenomedullin controls blood volume through the regulation of arginine vasopressin production and release

Brain-derived adrenomedullin controls blood volume through the regulation of arginine vasopressin production and release

The paraventricular nucleus of the hypothalamus – a potential target for integrative treatment of autonomic dysfunction

Decrease in arterial pressure induced by adrenomedullin in the hypothalamic paraventricular nucleus is mediated by nitric oxide and GABA

Contact Info

Product

Resources

About