Peripheral administration of selective GlyT2 inhibitor, oleoyl-D-lysine, is analgesic in neuropathic but not acute or inflammatory pain models in mice

Autor: Bruce Wilson, Julian Peiser-Oliver, Alexander Gillis, Sally Evans, Claudia Alamein, Shannon Mostyn, Susan Shimmon, Tristan Rawling, Macdonald Christie, Robert Vandenberg, Sarasa Mohammadi

Background and Purpose: Changes to spinal glycinergic signalling are a feature of pain chronification. Normalising those changes by inhibiting glycine transporter-2 (GlyT2) is a promising treatment strategy. However, existing GlyT2 inhibitors e.g. OR

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::ee6d05354385cbc4aaa040972253c758
https://doi.org/10.22541/au.163256291.16873032/v1

A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor

Autor: Paul F. Alewood, Eamonn Kelly, Katy J. Sutcliffe, Christophe Mallet, Andrew M. Piggott, Alexander Gillis, Paramjit Singh, Ranjala Ratnayake, Sarasa A. Mohammadi, Ernest Lacey, MacDonald J. Christie, Frank Fontaine, Richard B. Sessions, Meritxell Canals, Yan P. Du, Anna M. Wang, Setareh Sianati, Robert J. Capon, Zoltan Dekan, Arsalan Yousuf, Ai-Hua Jin, Michael Stewart

Publikováno v: Proceedings of the National Academy of Sciences of the United States of America
Dekan, Z, Sianati, S, Yousuf, A, Sutcliffe, K, Gillis, A, Mallet, C, Singh, P, Jin, A, Wang, A, Mohammadi, S, Stewart, M, Ratnayake, R, Fontaine, F, Lacey, E, Piggott, A, Du, Y, Canals, M, Sessions, R B, Kelly, E P, Capon, R, Alewood, P & Christie, M J 2019, ' A tetrapeptide class of biased analgesics from an Australian fungus targets the μ-opioid receptor ', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 44, pp. 22353-22358 . https://doi.org/10.1073/pnas.1908662116

Significance Agonists of the μ-opioid receptor (MOPr) are currently the gold standard for pain treatment. However, their therapeutic usage is greatly limited by side effects including respiratory depression, constipation, tolerance, and dependence.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e7d4d03fed007f2a4d12033bcdb9f177
http://europepmc.org/articles/PMC6825270

Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists

Autor: Michelle L. Halls, Julie Sanchez, Claudia Alamein, Meritxell Canals, Alexander Gillis, Frank Schmiedel, J. Robert Lane, Tristan A. Reekie, Preeti Manandhar, Michael Kassiou, Mark Connor, Andrea Kliewer, MacDonald J. Christie, Arisbel B. Gondin, Timothy A. Katte, Marina Santiago, Cornelius Krasel, Herman D. Lim, Stefan Schulz, Natasha L. Grimsey, Barrie Kellam, Sebastian Fritzwanker

Publikováno v: Science signaling. 13(625)

Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba9a0b0ae30a514d390609b92d3b0fab
https://pubmed.ncbi.nlm.nih.gov/32234959

Morphine-induced respiratory depression is independent of β-arrestin2 signalling

Autor: Stefan Schulz, Graeme Henderson, Rob Hill, Alexander Gillis, Eamonn Kelly, MacDonald J. Christie, Andrea Kliewer, Christopher P Bailey, Frank Schmiedel

Publikováno v: Br J Pharmacol
British Journal of Pharmacology
Kliewer, A, Gillis, A, Hill, R, Schmidel, F, Bailey, C, Kelly, E, Henderson, G, Christie, M J & Schulz, S 2020, ' Morphine-induced respiratory depression is independent of β-arrestin2 signalling ', British Journal of Pharmacology . https://doi.org/10.1111/bph.15004, https://doi.org/10.1111/bph.15004

BACKGROUND AND PURPOSE: GPCRs can signal through both G proteins and β-arrestin2. For the μ-opioid receptor, early experimental evidence from a single study suggested that G protein signalling mediates analgesia, whereas β-arrestin2 signalling med

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d783906f01696cd052f8780289471c26
https://pubmed.ncbi.nlm.nih.gov/32462692

Mediastinal Foregut Cyst Containing an Intramural Adrenal Cortical Rest: A Case Report and Review of Supradiaphragmatic Adrenal Rests

Autor: James R. Wright, D. Alexander Gillis

Publikováno v: Pediatric Pathology. 13:401-407

We present a case of a baby girl with a congenital cystic mediastinal mass which was excised at 20 months of age and was found to be a developmental foregut cyst of the gastroenteric type. Within the cyst wall was an adrenal cortical rest. Adrenal co

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ccb7c4b4aa1b349b5a77d94853022f0
https://doi.org/10.3109/15513819309048228