Chronotropic effect of D-Ala2,Leu5,Arg6-enkephalin (dalargin) is associated with activation of peripheral κ-opioid receptors

Abstract

Intravenous infusion of D-Ala2,Leu5,Arg6-enkephalin (dalargin) caused bradycardia in narcotized rats. This effect was not observed during opioid receptor blockade with naloxone, naloxone methiodide, and norbinaltorphimine. Dalargin and (-)-U-50,488 added to Krebs-Henseleit perfusion solution for isolated rat heart decreased heart rate. Ganglionic blocker hexamethonium potentiated the negative chronotropic effect of dalargin. The negative chronotropic effect of dalargin is probably associated with activation of cardiac kappa-opioid receptors. It should be noted that dalargin caused tachycardia in some animals. This reaction was not observed after treatment with hexamethonium. The positive chronotropic effect of dalargin is probably related to modulation of the parasympathetic autonomic nervous system. Agonists and antagonists of delta-opioid receptors caused persistent bradycardia. We hypothesized that selective delta-opioid antagonists exhibit properties of partial delta-receptor agonists.