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Serotonin (5‐HT) Receptor Expression and Function in the Kidney and Vasculature is Altered in the Streptozotocin (STZ) rat model of Diabetes Mellitus
Author(s) -
Bhaskaran Subha,
Singhal Sara,
BanesBerceli Amy
Publication year - 2013
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.27.1_supplement.917.1
Subject(s) - medicine , endocrinology , diabetes mellitus , receptor , kidney , streptozotocin , 5 ht receptor , serotonin
Diabetes is characterized by vascular and kidney damage. Accumulating evidence suggests that vasoactive substances such as 5‐HT stimulate these pathological processes and plasma levels of 5‐HT are elevated in diabetes. In recent clinical studies 5‐HT 2A receptor antagonists substantially decreased albuminuria in type 2 diabetic patients suggesting 5‐HT is mediating pathological processes in vivo . The molecular mechanisms behind the role of 5‐ HT and expression of 5‐HT receptors in vivo in normal and diabetic conditions are currently unknown. Utilizing male Sprague‐ Dawley rats in a type I model of diabetes we used Western blot and immunohistochemical (IHC) analyses to show a significant increase in the expression of 5‐HT 2B and 5‐HT 2A receptor proteins but not the 5‐HT 2C receptor in the diabetic rat kidney. Furthermore, our ex vivo myograph data suggests an increase in the activation of the 5‐HT‐induced intracellular signaling that can stimulate a potentiated contractile response in both thoracic aorta and renal artery in type‐1 diabetic rats which may lead to cardiovascular complications. Investigating both the mechanisms of 5‐HT‐induced intracellular signaling, functional consequences and the expression of 5‐HT receptors, is critical because targeted inhibition may reduce the risk of both kidney damage and vascular abnormality; critical in the treatment for chronic diabetic patients. (NHLBI R00 AKLB)