Uroguanylin increases Ca2+ concentration in astrocytes via guanylate cyclase C-independent signaling pathway

Scientific paper - Original scientific paper

• Author: Nikola Habek
• Author: Martina Ratko
• Author: Aleksandra Dugandžić
• Author's institution: University of Zagreb; School of Medicine; (Department of Physiology and Immunology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology

Abstract (english)

Aim: To investigate the cyclic guanosine monophosphate (cGMP)/guanylate cyclase C (GC-C)-independent signaling pathway in astrocytes, which are a suitable model due to their lack of GC-C expression.
-----
Methods: Patch clamp was performed and intracellular Ca2+ concentrations and pH were measured in primary astrocyte cultures and brain slices of wild type (WT) and GC-C knockout (KO) mice. The function of GC-C-independent signaling pathway in the cerebellum was determined by behavior tests in uroguanylin (UGN) KO and GC-C KO mice.
-----
Results: We showed for the first time that UGN changed intracellular Ca2+ levels in different brain regions of the mouse. In addition to the midbrain and hypothalamus, GC-C was expressed in the cerebral and cerebellar cortex. The presence of two signaling pathways in the cerebellum (UGN hyperpolarized Purkinje cells via GC-C and increased intracellular Ca2+ concentration in astrocytes) led to a different motoric function in GC-C KO and UGN KO mice, probably via different regulation of intracellular pH in astrocytes.
-----
Conclusion: The UGN effects on astrocytes via a Ca2+-dependent signaling pathway could be involved in the modulation of neuronal activity.

• Keywords (english): Animals; Astrocytes* / metabolism; Calcium*; Guanylate Cyclase / metabolism; Mice; Natriuretic Peptides; Receptors, Peptide; Signal Transduction
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Croatian Medical Journal
• Numbering: vol. 62, no. 3, pp. 250-263
• p-ISSN: 0353-9504
• e-ISSN: 1332-8166
• DOI: https://doi.org/10.3325/cmj.2021.62.250
• URN:NBN: urn:nbn:hr:105:258172
• Publication: 2021-06-30
• Document URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275953/
• Type of resource: Text
• Access conditions: Open access
• Created on: 2021-07-28 08:00:13