Effect of intracerebroventricular (ICV) injection of adrenomedullin and its interaction with NPY and CCK pathways on food intake regulation in neonatal layer-type chicks

Article

作者: Hassanpour, Shahin ; Alimohammadi, Samad ; Zahed, Maryam Soleymani

Adrenomedullin has various physiological roles including appetite regulation. The objective of present study was to determine the effects of ICV injection of adrenomedullin and its interaction with NPY and CCK receptors on food intake regulation. In experiment 1, chickens received ICV injection of saline and adrenomedullin (1, 2, and 3 nmol). In experiment 2, birds injected with saline, B5063 (NPY₁ receptor antagonist, 1.25 µg), adrenomedullin (3 nmol) and co-injection of B5063+adrenomedullin. Experiments 3 to 5 were similar to experiment 2 and only SF22 (NPY₂ receptor antagonist, 1.25 µg), SML0891 (NPY₅ receptor antagonist, 1.25 µg) and CCK₄ (1 nmol) were injected instead of B5063. In experiment 6, ICV injection of saline and CCK_8s (0.125, 0.25, and 0.5 nmol) were done. In experiment 7, chickens injected with saline, CCK_8s (0.125 nmol), adrenomedullin (3 nmol) and co-injection of CCK_8s+adrenomedullin. After ICV injection, birds were returned to their individual cages immediately and cumulative food intake was measured at 30, 60, and 120 min after injection. Adrenomedullin (2 and 3 nmol) decreased food intake compared to control group (P < 0.05). Coinjection of B5063+adrenomedullin amplified hypophagic effect of adrenomedullin (P < 0.05). The ICV injection of the CCK_8s (0.25 and 0.5 nmol) reduced food intake (P < 0.05). Co-injection of the CCK_8s+adrenomedullin significantly potentiated adrenomedullin-induced hypophagia (P < 0.05). Administration of the SF22, SML0891 and CCK₄ had no effect on the anorexigenic response evoked by adrenomedullin (P > 0.05). These results suggested that the hypophagic effect of the adrenomedullin is mediated by NPY₁ and CCK_8s receptors. However, our novel results should form the basis for future experiments.

2024-07-01·Chemical Biology & Drug Design

In silico optimization of analogs derived pro‐adrenomedullin peptide to evaluate antimicrobial potential

Article

作者: da Silva, Viviane G. ; Santos, Alexandre Duarte O. ; Cardoso, Marlon H. ; Rezende, Samilla B. ; Andrade, Isadora E. P. ; Oshiro, Karen G. N. ; Franco, Octávio L. ; Buccini, Danieli F. ; Pereira, Julia A. L. ; Quigua‐Orozco, Raquel M. ; Porto, William F. ; Macedo, Maria L. R.

Abstract:

Diverse computational approaches have been widely used to assist in designing antimicrobial peptides with enhanced activities. This tactic has also been used to address the need for new treatment alternatives to combat resistant bacterial infections. Herein, we have designed eight variants from a natural peptide, pro‐adrenomedullin N‐terminal 20 peptide (PAMP), using an in silico pattern insertion approach, the Joker algorithm. All the variants show an α‐helical conformation, but with differences in the helix percentages according to circular dichroism (CD) results. We found that the C‐terminal portion of PAMP may be relevant for its antimicrobial activities, as revealed by the molecular dynamics, CD, and antibacterial results. The analogs showed variable antibacterial potential, but most were not cytotoxic. Nevertheless, PAMP2 exhibited the most potent activities against human and animal‐isolated bacteria, showing cytotoxicity only at a substantially higher concentration than its minimal inhibitory concentration (MIC). Our results suggest that the enhanced activity in the profile of PAMP2 may be related to their particular physicochemical properties, along with the adoption of an amphipathic α‐helical arrangement with the conserved C‐terminus portion. Finally, the peptides designed in this study can constitute scaffolds for the design of improved sequences.

2024-06-01·British journal of pharmacology

Pharmacology of erenumab in human isolated coronary and meningeal arteries: Additional effect of gepants on top of a maximum effect of erenumab

Article

作者: Bussiere, Jeanine ; de Vries, Tessa ; Danser, A H Jan ; MaassenVanDenBrink, Antoinette ; van den Bogaerdt, Antoon ; Rubio-Beltrán, Eloísa ; Dammers, Ruben ; Snellman, Josefin

Abstract:

Background and Purpose:

Multiple drugs targeting the calcitonin gene‐related peptide (CGRP) receptor have been developed for migraine treatment. Here, the effect of the monoclonal antibody erenumab on CGRP‐induced vasorelaxation was investigated in human isolated blood vessels, as well as the effect of combining erenumab with the small molecule drugs, namely rimegepant, olcegepant, or sumatriptan.

Experimental Approach:

Concentration–response curves to CGRP, adrenomedullin or pramlintide were constructed in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments, incubated with or without erenumab and/or olcegepant. pA2 or pKb values were calculated to determine the potency of erenumab in both tissues. To study whether acutely acting antimigraine drugs exerted additional CGRP‐blocking effects on top of erenumab, HCA segments were incubated with a maximally effective concentration of erenumab (3 μM), precontracted with KCl and exposed to CGRP, followed by rimegepant, olcegepant, or sumatriptan in increasing concentrations.

Key Results:

Erenumab shifted the concentration‐response curve to CGRP in both vascular tissues. However, in HCA, the Schild plot slope was significantly smaller than unity, whereas this was not the case in HMMA, indicating different CGRP receptor mechanisms in these tissues. In HCA, rimegepant, olcegepant and sumatriptan exerted additional effects on CGRP on top of a maximal effect of erenumab.

Conclusions and Implications:

Gepants have additional effects on top of erenumab for CGRP‐induced relaxation and could be effective in treating migraine attacks in patients already using erenumab as prophylaxis.

项与重组人肾上腺髓质素(University of Miyazaki) 相关的新闻（医药）

2022-08-01

·BioSpace

Endothelial Function Biomarker Bioactive Adrenomedullin (bio-ADM) Enables Triage of Sepsis Patients in the Emergency Department

Bio-ADM is a biomarker for the assessment of endothelial dysfunction, a hallmark of sepsis, and has been widely studied in intensive care units (ICU) Clinical trial in the emergency department (ED) shows that bio-ADM is predictive of ICU admission and may be used for early stratification of unselected sepsis patients The published data show that high levels of bio-ADM are predicting the risk for multiple organ failure and mortality, while low levels are associated with ED discharge HENNIGSDORF, GERMANY / ACCESSWIRE / August 1, 2022 / The diagnostics company SphingoTec GmbH (SphingoTec) announces new findings that support the clinical value of the biomarker bio-ADM for triaging sepsis patients in ED, exceeding the prognostic performance of routine biomarkers. So far, the predictive potential of the innovative biomarker has been confirmed and used primarily in ICU. A new study, recently published, confirms its applicability in ED (1). A severe infection can quickly progress to sepsis - a life-threatening situation. Unfortunately, sepsis is difficult to diagnose and treat because it has a high range of forms and intensities. However, successful treatment is primarily time-dependent (2): an early diagnosis can save lives! In ED, it is still difficult to identify sepsis patients early, and assigning the correct further treatment is thus challenging. Adrenomedullin, a hormone that has homeostatic and regulatory effects on various body systems (3,4), as well as playing a role in hemodynamic regulation, and is measurable via the biomarker bioactive Adrenomedullin (bio-ADM), may help to bridge this gap. Biomarkers can provide information about the underlying causes of a disease and allow predictions about potential changes in patient condition in the next hours to days. Bio-ADM is an already known biomarker in intensive care units (5). Now, it has been tested in ED whether there was an association between bio-ADM and sepsis severity. Furthermore, it was examined whether bio-ADM would allow distinguishing between patients who could be discharged from ED from those who, for example, are at high risk for multiple organ failure due to sepsis and thus need to be transferred to the ICU. Prof. Olle Melander, Professor and Senior Physician, Lund University and Skåne University Hospital in Sweden, explains: "The results of our study suggest that bio-ADM is potentially an important clinical biomarker in ED and could be used to allow early triage of sepsis patients. We demonstrated that bio-ADM allows a significantly better prediction of the sepsis severity than other biomarkers. Accordingly, high bio-ADM levels in ED are associated with mortality, as well as the development of severe multiple organ failure, while low levels indicate that patients may be discharged". Dr. Andreas Bergmann, founder, and CSO of SphingoTec adds: "In ED, triage is of enormous importance to provide patients with the right treatment. The study results indicate that previous experiences with the biomarker bio-ADM in ICU could be transferred to ED. The ability of bio-ADM to identify high-risk patients thus could help ED physicians to optimize their decision-making and patient management." References: Lundberg OHM, Rosenqvist M, Bronton K, Schulte J, Friberg H, Melander O (2022) Bioactive adrenomedullin in sepsis patients in the emergency department is associated with mortality, organ failure, and admission to intensive care. PLoS ONE 17(4): e0267497. World Health Organization Improving the prevention, diagnosis and clinical management of sepsis 2017, April 13. Available from: Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993; 192(2):553-60. /10.1006/bbrc.1993.1451 Samson WK, Resch ZT, Murphy TC, Vargas TT, Schell DA. Adrenomedullin: Is There Physiological Relevance in the Pathology and Pharmacology? News Physiol Sci. 1999; 14:255-9, .1999.14.6.255 Lundberg OHM, Lengquist M, Spangfors M, Annborn M, Bergmann D, Schulte J, et al. Circulating bioactive adrenomedullin as a marker of sepsis, septic shock, and critical illness. Crit Care. 2020; 24 (1):636. About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) develops and markets innovative in vitro diagnostic (IVD) tests for novel and proprietary biomarkers for the diagnosis, prediction and monitoring of acute medical conditions. SphingoTec's proprietary biomarker portfolio includes bioactive Adrenomedullin (bio-ADM), a biomarker for real-time assessment of endothelial function in conditions like sepsis, and Proenkephalin (penKid), a biomarker for real-time assessment of kidney function. Dipeptidyl Peptidase 3 (DPP3), a biomarker for cardiac depression. IVD tests for SphingoTec's biomarkers are made available as sphingotest® microtiter plate tests as well as point-of-care tests on the Nexus IB10 immunoassay platform by SphingoTec's subsidiary Nexus Dx Inc. (San Diego, CA, USA). The Nexus IB10 portfolio is complemented by established and commonly used biomarker tests for acute and critical care such as PCT, Troponin, NT-proBNP, D-Dimer, TSH and others. Media contact: Dr. Ulrike Glaubitz Senior Public Relations Specialist SphingoTec GmbH Neuendorfstr. 15 A 16761 Hennigsdorf Tel. +49-3302-20565-113 SOURCE: SphingoTec GmbH View source version on accesswire.com:

100 项与重组人肾上腺髓质素(University of Miyazaki) 相关的药物交易

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