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On the Mechanism of Flow Sensing by Guinea Pig Carotid Endothelial Cells
Author(s) -
EspinosaTanguma Ricardo,
HernándezMéndez Aurelio
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb319
Subject(s) - bradykinin , receptor , mapk/erk pathway , extracellular , g protein coupled receptor , microbiology and biotechnology , chemistry , medicine , endocrinology , biology , signal transduction
It is known that luminal facing endothelial G‐protein coupled receptors (GPCRs) are affected by flow. In human blood vessels bradykinin produces a relaxing effect whereas in guinea pig its effect is vasoconstrictive and affected by flow. Objetive to study the mechanism by which flow is sensed by endothelial cells. Methods we have used guinea pig carotid arteries to evaluate the effect of flow on the contractile response to bradykinin and cultured carotid endothelial cells to know the expression pattern of p‐SRC and p‐ERK in response to flow. Results We have found that in guinea pig carotid artery the flow‐dependent vasoconstrictive effect of bradykinin is augmented by 5 min luminal exposure to heparinase or alfa‐chymotrypsin enzymes suggesting that the flow sensor of the bradykinin receptor (BR) is associated to a carbohydrate residue and/or a protein segment of the receptor present in the extracellular face of the plasma membrane. By looking at the available molecular structure of the BR we have identified a segment of the N‐terminus that could be acting as the flow sensor by a very simple physical mechanism. On the other hand, by using carotid cultured endothelial cells we have found that flow decreases the expression of p‐SRC protein and does not change the p‐ERK expression. Conclusions the mechanism by which flow is sensed by endothelial cells is still on debate. However, one mechanism for sensing the flow could be located at the extracellular segment of the protein receptor. The N‐terminus segment of the BR could move depending on the flow velocity and, as a consequence, increasing or decreasing the availability of the BR to its ligand. Support or Funding Information Supported by Conacyt 223350 to RET. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .