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1. Signalling by CGRP and Adrenomedullin in the Cerebellum and Other Systems

Author

David Poyner, Heather Cater, Nick Hartell, Alex Conner, Debbie Hay, Steve Howitt, and Dave Smith

Subjects
Technology, Medicine, Science
Abstract

The best characterised signalling pathway activated by both CGRP and adrenomedullin is stimulation of adenylate cyclase via Gs. However, it is clear that in some circumstances the peptides can activate other signal transduction pathways, e.g., increases in intracellular calcium. Many of these signalling pathways can be observed in cultured cells but it is important also to examine isolated tissues to discover the full repertoire of transduction events. In the rat cerebellum there are receptors that respond to both CGRP and adrenomedullin. These seem to be located postsynaptically on Parallel Fibre nerve terminals and modulate transmission to Purkinje cells. Adrenomedullin acts via cAMP, apparently to augment neurotransmitter release. By contrast, CGRP decreases transmitter release, via a non-cAMP mediated pathway. We are currently examining the role of NO and tyrosine kinases in the responses to these peptides.

Published
2001
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2. Molecular mechanisms governing aquaporin relocalisation

Author

Andrea Markou, Lucas Unger, Mohammed Abir-Awan, Ahmed Saadallah, Andrea Halsey, Zita Balklava, Matthew Conner, Susanna Törnroth-Horsefield, Stuart D. Greenhill, Alex Conner, Roslyn M. Bill, Mootaz M. Salman, and Philip Kitchen

Subjects
Osmosis, Protein Transport, Cell Membrane, Biophysics, Animals, Humans, Protein Isoforms, Water, Cell Biology, Plants, Aquaporins, Biochemistry
Abstract

The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis.

Published
2022

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