pituitrin and apelin-13-peptide

Vasopressin exerts robust influences on social communication and behavior in humans. Apelin is a relatively novel neuropeptide that could counteract vasopressin's actions and has been shown to be closely related with a broad range of physiological functions. Abnormalities in vasopressin and apelin have been detected in a variety of psychiatric disorders, but their relation to attention-deficit hyperactivity disorder (ADHD) is unknown. In the present study, we explored the plasma levels of vasopressin and apelin-13 in children with ADHD.. Thirty-four children with ADHD and 36 healthy controls were enrolled in this study. The severity of ADHD symptoms was assessed via Conners' Parent Rating Scale and Conners' Teacher Rating Scale. Plasma levels of vasopressin and apelin-13 were measured using commercial enzyme-linked immunosorbent assay kits.. The mean plasma apelin-13 levels were significantly higher in male children with ADHD than in male control subjects; no significant difference was found between the groups for plasma apelin-13 levels in girls or in the entire subject cohort. Plasma vasopressin levels did not show any significant differences between groups. There were no significant correlations between plasma levels of these neuropeptides and scores for Conners' Parent Rating Scale and Conners' Teacher Rating Scale.. Our results suggest a sex-specific association between plasma apelin-13 levels and ADHD. Apelin-13 may play a role in the etiopathogenesis of ADHD either with a direct impact on the apelin receptor or via its opposing effect on the vasopressinergic system.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Sex Factors; Vasopressins

The apelinergic system has a widespread expression in the central nervous system (CNS) including the paraventricular nucleus, supraoptic nucleus and median eminence, and isolated cells of the anterior lobe of the pituitary. This pattern of expression in hypothalamic nuclei known to contain corticotrophin-releasing factor (CRF) and vasopressin (AVP) and to co-ordinate endocrine responses to stress has generated interest in a role for apelin in the modulation of stress, perhaps via the regulation of hormone release from the pituitary. In this study, to determine whether apelin has a central role in the regulation of CRF and AVP neurones, we investigated the effect of i.c.v. administration of pGlu-apelin-13 on neuroendocrine function in male mice pre-treated with the CRF receptor antagonist, alpha-helical CRF(9-41), and in mice-lacking functional AVP V1b receptors (V1bR KO). Administration of pGlu-apelin-13 (1 mg/kg i.c.v.) resulted in significant increases in plasma ACTH and corticosterone (CORT), which were significantly reduced by pre-treatment with alpha-helical CRF(9-41), indicating the involvement of a CRF-dependent mechanism. Additionally, pGlu-apelin-13-mediated increases in both plasma ACTH and CORT were significantly attenuated in V1bR KO animals when compared with wild-type controls, indicating a role for the vasopressinergic system in the regulation of the effects of apelin on neuroendocrine function. Together, these data confirm that the in vivo effects of apelin on hypothalamic-pituitary-adrenal neuroendocrine function appear to be mediated through both CRF- and AVP-dependent mechanisms.

Topics: Animals; Corticotropin-Releasing Hormone; Hormone Antagonists; Hydrocortisone; Hypothalamo-Hypophyseal System; Intercellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurosecretory Systems; Peptide Fragments; Pituitary-Adrenal System; Receptors, Corticotropin-Releasing Hormone; Receptors, Vasopressin; Signal Transduction; Vasopressins

Apelin, a novel peptide originally isolated from bovine stomach tissue extracts, is widely but selectively distributed throughout the nervous system. Vasopressin and oxytocin are synthesized in the magnocellular neurons of the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus, which are apelin-rich regions in the central nervous system. We made extracellular electrophysiological recordings from the transpharyngeally exposed SON of urethane-anaesthetized rats to assess the role of apelin in the control of the firing activity of identified magnocellular vasopressin and oxytocin neurons in vivo. Apelin-13 administration onto SON neurons via microdialysis revealed cell-specific responses; apelin-13 increased the firing rates of vasopressin cells but had no effect on the firing rate of oxytocin neurons. A direct excitatory effect of apelin-13 on vasopressin cell activity is also supported by our in vitro studies showing depolarization of membrane potential and increase in action potential firing. To assess the effects of apelin-13 on somatodendritic peptide release, we used in vitro release studies from SON explants in combination with highly sensitive and specific RIA. Apelin-13 decreases basal (by 78%; P < 0.05; n = 6) and potassium-stimulated (by 57%; P < 0.05; n = 6) vasopressin release but had no effect on somatodendritic oxytocin release. Taken together, our data suggest a local autocrine feedback action of apelin on magnocellular vasopressin neurons. Furthermore, these data show a marked dissociation between axonal and dendritic vasopressin release with a decrease in somatodendritic release but an increase in electrical activity at the cell bodies, indicating that release from these two compartments can be regulated wholly independently.

Topics: Animals; Dendrites; Electrophysiology; Female; Hypothalamus; Intercellular Signaling Peptides and Proteins; Neurons; Oxytocin; Peptide Fragments; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Rats, Wistar; Vasopressins

Dysregulation of the vasopressin (AVP) system has been implicated in the pathogenesis of autistic spectrum disorder (ASD). Apelin is a recently discovered neuropeptide that could counteract AVP actions and whose receptors are colocalized with vasopressin in hypothalamic magnocellular neurons. Aims of the present study were to investigate circulating levels of apelin in patients with ASD and to assess their correlation with plasma AVP concentrations.. Plasma levels of apelin and AVP were measured in a total of 18 patients with ASD and 21 age- and gender-matched healthy comparison subjects. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms.. Significantly reduced levels of apelin (p < 0.001) and elevated concentrations of AVP (p = 0.02) were found in ASD patients as compared to controls. Additionally, a significant inverse correlation between apelin and AVP levels was found within the ASD group (r = -0.61; p = 0.007), but not in healthy participants (r = -0.26; p = 0.25). Multivariate linear regression analysis showed that only AVP concentrations independently predicted apelin values in ASD individuals (beta = -0.42, t = 2.63, p = 0.014). No correlation was seen between apelin levels and CARS scores (r = -0.10; p = 0.68).. Our findings of a significantly reduced peripheral level of apelin coupled with elevated AVP point to a subtle but definite vasopressinergic dysfunction in autism that could play a role in the etiopathophysiology of this disorder in humans.

Topics: Adolescent; Adult; Autistic Disorder; Case-Control Studies; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Vasopressins