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0031-6997/07/5901-88-123$7.00
Pharmacol Rev 59:88-123, 2007

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The Endomorphin System and Its Evolving Neurophysiological Role

Jakub Fichna, Anna Janecka, Jean Costentin and Jean-Claude Do Rego

Laboratory of Experimental Neuropsychopharmacology, Centre National de la Recherche Scientifique-Formation de Recherche en Evolution 2735, European Institute of Peptide Research (Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23), Faculty of Medicine and Pharmacy, Institute of Biomedical Research, University of Rouen, Rouen, France (J.F., J.C., J.-C.d.R.); and Laboratory of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland (J.F., A.J.)

Abstract
I. Introduction
II. Structure-Activity Relationship Studies
III. Distribution
IV. Receptors
V. Enzymatic Degradation
VI. Neurophysiological Role
    A. Biological Effects of Endomorphins
        1. Pain.
            a. Central administration of endomorphins.
            b. Peripheral administration of endomorphins.
        2. Tolerance.
        3. Physical Dependence.
        4. Effects on Locomotor Activity.
        5. Behavioral Sensitization.
        6. Drug Addiction, Mechanism of Reward.
        7. Psychiatric disorders.
            a. Stress.
            b. Anxiety.
            c. Depression and other psychiatric disorders.
        8. Social Defeat.
        9. Food Intake.
        10. Sexual Behavior.
        11. Learning and Memory.
        12. Effects on Cardiovascular System.
        13. Effects on Respiratory System.
        14. Effects on Gastrointestinal Tract.
    B. Endomorphins, Neurotransmitters, and Neurohormones
        1. Modulation of Dopamine Transmission.
        2. Modulation of Noradrenaline Transmission.
        3. Modulation of Serotonin Transmission.
        4. Modulation of Acetylcholine Transmission.
        5. Modulation of Neurohormone Release.
VII. Conclusions
Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are two endogenous opioid peptides with high affinity and remarkable selectivity for the µ-opioid receptor. The neuroanatomical distribution of endomorphins reflects their potential endogenous role in many major physiological processes, which include perception of pain, responses related to stress, and complex functions such as reward, arousal, and vigilance, as well as autonomic, cognitive, neuroendocrine, and limbic homeostasis. In this review we discuss the biological effects of endomorphin-1 and endomorphin-2 in relation to their distribution in the central and peripheral nervous systems. We describe the relationship between these two µ-opioid receptor-selective peptides and endogenous neurohormones and neurotransmitters. We also evaluate the role of endomorphins from the physiological point of view and report selectively on the most important findings in their pharmacology.

Address correspondence to: Dr. Jean-Claude do Rego, Laboratory of Experimental Neuropsychopharmacology, CNRS FRE 2735, IFRMP 23, Faculty of Medicine & Pharmacy, University of Rouen, 22, Boulevard Gambetta, 76183 Rouen cedex, France. E-mail: jean-claude.dorego{at}univ-rouen.fr




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