title: Opioid Facilitation of β-Adrenergic Blockade: A New Pharmacological Condition?
abstract: Recently, propranolol was suggested to prevent hyperlactatemia in a child with hypovolemic shock through β-adrenergic blockade. Though it is a known inhibitor of glycolysis, propranolol, outside this observation, has never been reported to fully protect against lactate overproduction. On the other hand, literature evidence exists for a cross-talk between β-adrenergic receptors (protein targets of propranolol) and δ-opioid receptor. In this literature context, it is hypothesized here that anti-diarrheic racecadotril (a pro-drug of thiorphan, an inhibitor of enkephalinases), which, in the cited observation, was co-administered with propranolol, might have facilitated the β-blocker-driven inhibition of glycolysis and resulting lactate production. The opioid-facilitated β-adrenergic blockade would be essentially additivity or even synergism putatively existing between antagonism of β-adrenergic receptors and agonism of δ-opioid receptor in lowering cellular cAMP and dependent functions.
authors.affiliation: Inserm, Laboratory of Molecular Biology and Biochemistry, Hormonology Metabolism Nutrition and Oncology, Center of Biology and Pathology, CHRU Lille, and RADEME EA 7364, Faculty of Medicine, University of Lille 2, Lille 59037, France. joseph.vamecq@inserm.fr.
authors.forename: Joseph
authors.initials: J
authors.lastname: Vamecq
authors.affiliation: Centre de Référence Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Jeanne de Flandre Hospital, CHRU Lille, and RADEME EA 7364, Faculty of Medicine, University Lille 2, Lille 59037, France. karine.mention@chru-lille.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Mention-Mulliez
authors.affiliation: Pediatric Critical Care Unit, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France. francis.leclerc@chru-lille.fr.
authors.forename: Francis
authors.initials: F
authors.lastname: Leclerc
authors.affiliation: Centre de Référence Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Jeanne de Flandre Hospital, CHRU Lille, and RADEME EA 7364, Faculty of Medicine, University Lille 2, Lille 59037, France. dries.dobbelaere@chru-lille.fr.
authors.forename: Dries
authors.initials: D
authors.lastname: Dobbelaere
keywords: G protein; Na+/K+ ATPase; cAMP; glycolysis disruption; lactate; protein kinase A; shock; β-adrenergic receptor; δ-opioid receptor