http://www.ncbi.nlm.nih.gov/pubmed/26786146
Gulati A1.
Abstract
The
ET family consists of three isopeptides (ET-1, ET-2 and ET-3) that
produce biological actions by acting on two types of receptors (ETA and
ETB). Stimulation of ETA receptors produces potent vasoconstrictor
effect, while activation of ETB receptors causes vasodilation by
releasing nitric oxide (NO) and prostacyclins. In the central nervous
system (CNS) ETA receptors are potent constrictors of the cerebral
vasculature and appear to contribute in the causation of cerebral
ischemia. ETA receptor antagonists have been found to be effective in
animal model of cerebral ischemia; however, clinical studies have shown
no efficacy.(Well don't give up, figure out why) Mitochondrial functions are critically important for
several neural development processes such as neurogenesis, axonal and
dendritic growth, and synaptic formation. ET appears to impair
mitochondrial functions through activation of ETA receptors. On the
other hand, blocking ETB receptors has been shown to trigger apoptotic
processes by activating intrinsic mitochondrial pathway. Mitochondria
are important for their role in molecular regulation of neurogenesis and
angiogenesis. Stimulation of ETB receptors in the adult ischemic brain
has been found to promote angiogenesis and neurogenesis mediated through
vascular endothelial growth factor (VEGF) and nerve growth factor
(NGF). It will be interesting to investigate the effect of ETB receptor
stimulation on mitochondrial functions in the CNS following cerebral
ischemia. In the CNS stimulation of ETB receptors has a beneficial
effect in animal models of stroke. Since angiogenesis and neurogenesis
have recently been implicated in cerebral ischemia, the positive effect
of stimulating ETB receptors in cerebral ischemia may be mediated
through mitochondrial functions.
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