Premium
Effects of metformin on spontaneous and cholinergic contractions of the rat bladder
Author(s) -
Peuler Jacob D.,
Senn Christopher J.,
Phelps Laura E.
Publication year - 2011
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.25.1_supplement.1020.2
Subject(s) - metformin , cholinergic , acetylcholine , endocrinology , diabetes mellitus , medicine , urine , urination , chemistry , urinary system
Diabetes causes autonomic neuropathy which impairs bladder parasympathetic release of acetylcholine (ACh) during the active phase of micturation, resulting in inadequate voiding of urine. Diabetes also causes incontinence which is a problem during storage of urine in the resting bladder. Previously we reported that a high (10 millimolar) concentration of the antidiabetic drug metformin can rapidly enhance rat bladder contractile responses to ACh (FASEB J. 22:916.6, 2008).We tested whether long‐term (4‐hour) pretreatment with a lower, more therapeutically‐relevant concentration of metformin (100 micromolar) would do the same. First, after 4 hours the 100 micromolar metformin exerted contrasting effects on cholinergic (ACh‐induced) vs non‐cholinergic (e.g. K‐induced) contractions of isolated rat bladder tissues (p < 0.05), tending to enhance the former (by 31–51%) and inhibit the latter (by 9–18%). Second, during the pretreatment period the 100 micromolar metformin interacted with pretreatment time (p < 0.05) to specifically increase amplitudes of resting spontaneous contractile activity (after 2–4 hours) without altering the midpoint level of resting contractile tone or the frequency of the spontaneous activity. These findings may be relevant to potential effects of metformin on the abovementioned clinical problems in diabetic patients. Support: Midwestern University.