engleski

The effects of natriuretic peptides on the bradykinin signaling in primary culture of neurons and astrocytes

Blockage of cerebral arteries leads to stroke and subsequent development of cerebral edema. In vivo experiments in a mouse model of stroke showed that i.v. application of natriuretic peptide prevents the formation of brain lesions. In this study we investigated the effect of an agonist of guanylate cyclase A (GC-A), guanylate cyclase B (GC-B) and guanylate cyclase C (GC-C) on primary cultures of astrocytes and neurons, and the effect of natriuretic peptides on the bradykinin signaling system using the patch clamp technique. Binding of bradykinin to B2R receptor in neurons and astrocytes leads to depolarization of the cell membrane, via increasing of intracellular Ca2+ concentration and activation of Ca2+-dependent Cl- channel. GC-A agonists and GC-C agonists inhibit bradykinin dependent depolarization of the cell membrane and release of Ca2+, while GC-B agonist does not. The mechanism of interaction of signaling pathways of GC-A and GC-C agonists and bradykinin in neurons and astrocytes is conducted by RGS protein regulation. Natural antagonism of GC-A and GC-C agonists on B2R signaling pathway shown in cellular models of neurons and astrocytes can be used to develop new therapeutic approach to the treatment of pathophysiological conditions mediated by bradykinin, such as ischemic brain injury.

cerebral edema; bradykinin; natriuretic peptides

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