1. CCKA, but not CCKB, agonists suppress the hyperlocomotion induced by endogenous enkephalins, protected from enzymatic degradation by systemic RB 101
- Author
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Bernard P. Roques, Valérie Daugé, P. J. Corringer, Pharmacochimie moléculaire et structurale, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), We wish to thank Dr. A. Beaumont and Dr.J.Vierek for the stylistic revision of the paper, and C. Dupuis for her assistance in drafting it. We are grateful to S.Turcaud and P. Coric for the synthesis of RB 101., Cova Rodrigues, Ana, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,Enkephalin ,Narcotic Antagonists ,[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,RB-101 ,Devazepide ,Inhibitor of enkephalin degradation ,MESH: Amino Acid Sequence ,Toxicology ,Biochemistry ,MESH: Benzodiazepinones ,Behavioral Neuroscience ,Mice ,0302 clinical medicine ,Interactions between CCK and enkephalins ,MESH: Enkephalins ,MESH: Animals ,Disulfides ,Enzyme Inhibitors ,MESH: Cholecystokinin ,MESH: Peptide Fragments ,MESH: Devazepide ,0303 health sciences ,Benzodiazepinones ,MESH: Receptors, Cholecystokinin ,Chemistry ,digestive, oral, and skin physiology ,Enkephalins ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Naltrexone ,CCKA and CCKB agonists ,MESH: Motor Activity ,[SDV] Life Sciences [q-bio] ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,MESH: Enzyme Inhibitors ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,MESH: Naltrexone ,MESH: Narcotic Antagonists ,Cholecystokinin ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Agonist ,Locomotor activity ,medicine.medical_specialty ,medicine.drug_class ,Phenylalanine ,Molecular Sequence Data ,Motor Activity ,03 medical and health sciences ,MESH: Phenylalanine ,Naltrindole ,Internal medicine ,medicine ,Animals ,MESH: Disulfides ,Amino Acid Sequence ,Opioid peptide ,MESH: Mice ,Biological Psychiatry ,030304 developmental biology ,Pharmacology ,MESH: Molecular Sequence Data ,Antagonist ,Peptide Fragments ,MESH: Male ,Endocrinology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Receptors, Cholecystokinin ,Physiological agonism and antagonism ,030217 neurology & neurosurgery - Abstract
International audience; Interactions between CCKergic and enkephalinergic systems were studied in mice using behavioral responses measured in Animex. The hyperlocomotion induced by 5 mg/kg of RB 101, a mixed inhibitor of enkephalin-degrading enzymes able to cross the blood-brain barrier, was previously shown to be mediated by delta-opioid receptor stimulation. The IP administration of a CCKA agonist, Boc-Tyr-Lys-(CONH-o-tolyl)-Asp-Phe-NH2 (0.1, 1, 10 micrograms/kg), suppressed the hyperlocomotion produced by IV injection of 5 mg/kg of RB 101. The effect of the CCKA agonist was suppressed by a selective CCKA antagonist, devazepide, injected IP at doses of 20 and 200 micrograms/kg and was potentiated by the selective delta-opioid antagonist naltrindole at the doses of 0.03 mg/kg. IP injection of the selective CCKB agonist BC 264 (0.1-1 mg/kg) did not modify the RB 101-induced hyperlocomotor effect. These results reinforce the observed physiological antagonism between the endogenous CCK and opioid systems but are at variance with the responses measured in stressful conditions. It is concluded that CCKA, but not CCKB, receptor activation counteracts the opioid-related hyperlocomotion.
- Published
- 1995
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