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Effects of metformin on bethanechol‐induced bladder contractions
Author(s) -
Peuler Jacob Dale,
Curtis Jeremy K,
Phelps Laura E
Publication year - 2012
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.26.1_supplement.1049.2
Subject(s) - bethanechol , metformin , smooth muscle , urinary bladder , medicine , endocrinology , pharmacology , chemistry , diabetes mellitus , receptor , muscarinic acetylcholine receptor
By contracting detrusor smooth muscle bethanechol can treat urinary retention in patients with diabetic bladder dysfunction. Previously, we reported that millimolar levels of the antidiabetic drug metformin can markedly inhibit such contractions in the rat bladder. In the present work, we find that levels ≤ 200 micromolar do not do so suggesting that therapeutically‐relevant levels of metformin (as seen in plasma of patients) will not interfere with the ability of bethanechol to contract and thus empty the bladder in patients who need it. The mechanism whereby metformin (at ≥1 millimolar) inhibits bethanechol‐induced bladder smooth muscle contractions is unknown. We also found that, at its EC50 of 5 millimolar, metformin's inhibition of bethanechol contractions was significantly antagonized (p<0.05) by 4‐aminopyridine (4AP) and tetraethylammonium (TEA). Therefore, we suspect that such metformin inhibits bethanechol contractions in bladder by activating potassium (K) efflux through both 4AP‐sensitive and TEA‐sensitive K channels. Support: MWU Biomedical Science Masters Program.