title: Tetramethylammonium is a muscarinic agonist in rat heart.
abstract: Studies were designed to determine if tetramethylammonium (TMA), a quaternary amine that structurally resembles the cationic portion of acetylcholine, can affect cardiac function by acting on muscarinic receptors. Experiments examined effects of this cation on 1) the spontaneous beating rate of right atrial preparations isolated from rats, 2) force of contraction in isoproterenol-treated (0.1 microM) rat papillary muscle, and 3) quinuclidinyl benzilate ([3H]QNB) binding to rat ventricular membranes. TMA elicited concentration-dependent (0.5-50 mM) negative chronotropic and negative inotropic actions that were antagonized by the muscarinic receptor antagonist atropine. Radioligand studies showed that TMA acts as both a competitive and noncompetitive antagonist of [3H]QNB binding; the apparent dissociation constant for [3H]QNB was increased (0.092 +/- 0.025 nM in the absence of TMA; 1.14 +/- 0.204 nM in the presence of 50 mM TMA), whereas binding site density was decreased (148 +/- 26 and 65 +/- 4 fmol/mg in the absence and presence of 50 mM TMA, respectively). These results suggest that extracellular TMA can alter the function of rat heart by stimulating muscarinic receptors. This action should be considered when using this quaternary amine as a cation substitute.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Kennedy
authors.forename: R P
authors.initials: RP
authors.lastname: Wyeth
authors.forename: P
authors.initials: P
authors.lastname: Gerner
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: H J
authors.initials: HJ
authors.lastname: Fontenot
authors.forename: E
authors.initials: E
authors.lastname: Seifen
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002462:Cell Membrane; D018678:Cholinergic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008536:Meglumine / Q000494:pharmacology; D015999:Multivariate Analysis; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D018678:Cholinergic Agents; D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D008536:Meglumine; D001285:Atropine; C027917:tetramethylammonium