Inhibition of Protein Kinases AKT and ERK1/2 Reduce the Carotid Body Chemoreceptor Response to Hypoxia in Adult Rats.

Abstract

The carotid body is the main mammalian oxygen-sensing organ regulating ventilation. Despite the carotid body is subjected of extensive anatomical and functional studies, little is yet known about the molecular pathways signaling the neurotransmission and neuromodulation of the chemoreflex activity. As kinases are molecules widely involved in motioning a broad number of neural processes, here we hypothesized that pathways of protein kinase B (AKT) and extracellular signal-regulated kinases ½ (ERK1/2) are implicated in the carotid body response to hypoxia. This hypothesis was tested using the in-vitro carotid body/carotid sinus nerve preparation ("en bloc") from Sprague Dawley adult rats. Preparations were incubated for 60 min in tyrode perfusion solution (control) or containing 1 μM of LY294002 (AKT inhibitor), or 1 μM of UO-126 (ERK1/2 inhibitor). The carotid sinus nerve chemoreceptor discharge rate was recorded under baseline (perfusion solution bubbled with 5 % CO(2) balanced in O(2)) and hypoxic (perfusion solution bubbled with 5 % CO(2) balanced in N(2)) conditions. Compared to control, both inhibitors significantly decreased the normoxic and hypoxic carotid body chemoreceptor activity. LY294002- reduced carotid sinus nerve discharge rate in hypoxia by about 20 %, while UO-126 reduces the hypoxic response by 45 %. We concluded that both AKT and ERK1/2 pathways are crucial for the carotid body intracellular signaling process in response to hypoxia.

• Authors: Pablo Iturri, Vincent Joseph, Gloria Rodrigo, Aida Bairam, Jorge Soliz
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 860 Pg. 269-77 ( 2015) ISSN: 0065-2598 [Print] United States
• PMID: 26303491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butadienes
• Chromones
• Morpholines
• Nitriles
• U 0126
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Butadienes (pharmacology)
• Carotid Body (physiology)
• Chromones (pharmacology)
• Hypoxia (physiopathology)
• Male
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, physiology)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, physiology)
• Morpholines (pharmacology)
• Nitriles (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, physiology)
• Rats
• Rats, Sprague-Dawley