title: Enkephalins have a direct positive inotropic effect on cultured cardiac myocytes.
abstract: Enkephalins have peripheral vascular effects, and enkephalinergic innervation of the heart has been reported. To determine whether enkephalins have direct effects on myocardium, we studied the effects of [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin on amplitude of contraction (measured with an optical-video system) in spontaneously beating monolayer cultures of chicken embryo ventricular cells, a preparation devoid of intact neural elements. [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin as well as [Met5]- and [Leu5]enkephalin increased contractility in a concentration-dependent manner. The enkephalin-induced maximal contractile effects were 28% and 30% above control, with EC50 values of 0.53 and 0.17 microM for [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin, respectively. The positive inotropic effect was antagonized by naloxone but not by propranolol, phentolamine, diphenhydramine, or cimetidine. Naloxone alone had no effect on contractility at a concentration (0.1 microM) that blocked positive inotropic effects of [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin. To demonstrate the presence of opiate receptors, we studied [3H]naloxone binding in homogenates of cultured chicken embryo ventricular cells. Analysis of binding curves under equilibrium conditions indicated that [3H]naloxone bound specifically to membranes of cultured heart cells with KD = 18.5 +/- 5.4 nM and Bmax = 46.8 +/- 11.7 fmol/mg of protein. We conclude that enkephalins exert a direct positive inotropic effect on cultured heart cells, increasing contractile state via specific opiate receptors.
authors.forename: S
authors.initials: S
authors.lastname: Laurent
authors.forename: J D
authors.initials: JD
authors.lastname: Marsh
authors.forename: T W
authors.initials: TW
authors.lastname: Smith
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002642:Chick Embryo; D004745:Enkephalins / Q000378:metabolism / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism
chemical_list: D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D011433:Propranolol; D007545:Isoproterenol; D002118:Calcium