Premium
Effects of metformin on bethanechol‐induced contractions of the lower esophageal sphincter (653.8)
Author(s) -
Peuler Jacob,
Murphy Patrick,
Phelps Laura
Publication year - 2014
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.28.1_supplement.653.8
Subject(s) - bethanechol , metformin , muscarinic acetylcholine receptor , agonist , endocrinology , medicine , esophagus , smooth muscle , pilocarpine , tetraethylammonium , potassium channel , pharmacology , receptor , chemistry , diabetes mellitus , potassium , organic chemistry , psychiatry , epilepsy
Metformin is widely used in the treatment of diabetes. We have shown 1) that at millimolar concentrations it can markedly inhibit contractions of the isolated rat bladder as induced by the muscarinic receptor agonist bethanechol and 2) that this effect can be antagonized by the potassium (K) channel blockers tetraethylammonium (TEA) and 4‐aminopyridine (4AP) but not barium or glyburide (The FASEB Journal 2012 ; 26 :1049.2). Thus, metformin may be opening some but not other subpopulations of K channels known to exist in smooth muscle cell membranes of the bladder wall. We tested for these same effects in the lower esophageal sphincter of the rat because 1) by contracting this tissue bethanechol is used to treat gastroesophageal reflux disease (which is common in diabetic patients) and 2) metformin is known to reach millimolar concentrations in gastrointestinal tissues (including the esophagus) after standard oral dosing. Our results were the same as we observed previously in rat bladder. Thus, metformin’s ability to inhibit muscarinic receptor‐mediated smooth muscle contractions may be related in general to an ability to open both TEA‐sensitive and 4AP‐sensitive K channels in all smooth muscle cell membranes.