Premium
Activation of AMP‐activated protein kinase (AMPK) increases phenylephrine mediated contraction in murine corpus cavernosum
Author(s) -
Labazi Hicham,
Wynne Brandi M.,
Webb R. Clinton
Publication year - 2009
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.23.1_supplement.781.1
Subject(s) - endocrinology , ampk , medicine , phenylephrine , enos , chemistry , protein kinase a , sodium nitroprusside , contraction (grammar) , amp activated protein kinase , phosphorylation , nitric oxide , biochemistry , nitric oxide synthase , blood pressure
AMP‐activated protein kinase (AMPK) is a serine/threonine kinase that was shown to phosphorylate eNOS at ser1177 and also at thr495. Although the role of AMPK in the vascular system has been the recent subject of much investigation, its role in erectile tissue has yet to be defined. Using a pharmacological approach, our objective was to elucidate its role in the corpus cavernosum. A concentration response curve (CRC) to 5‐aminoimidazole‐4‐carboxamide‐1‐b‐riboside (AICAR), a known AMPK activator, in phenylephrine (Phe) contracted corpus cavernosal strips did not cause relaxation, even at high concentrations (3mM). However, with AICAR (1mM) pre‐incubation, an increase in phenylephrine‐mediated contraction was observed compared to control (1.22±0.06 vs. 0.71± 0.03). The CRC to U‐46619 (a thromboxane receptor agonist) and endothelin‐1 did not show any significant difference in contraction between the two groups. However, with AICAR pre‐incubation, there was a significant attenuation of acetylcholine‐mediated relaxation (57.17± 2.87 % in Aicar vs. 71.66± 2.53% in control) and also relaxation mediated by sodium nitroprusside (43.24± 2.59 % in Aicar vs. 60.01± 2.47% in control). We speculate that activation of AMPK in penile tissue leads to phosphorylation of eNOS at Thr 495 producing inactivation of eNOS. Thus, NO bioavailability is reduced resulting in decreasing relaxation and increasing contraction.