Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.Enkephalin, Methionine: One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.Enkephalin, Leucine: One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.Enkephalin, Ala(2)-MePhe(4)-Gly(5)-: An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.Enkephalin, Leucine-2-Alanine: A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the PRO-OPIOMELANOCORTIN precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; OPIOID PEPTIDES is used for the broader group.Leucine Zippers: DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Receptors, Opioid, delta: A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.Receptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.Ethylketocyclazocine: A kappa opioid receptor agonist. The compound has analgesic action and shows positive inotropic effects on the electrically stimulated left atrium. It also affects various types of behavior in mammals such as locomotion, rearing, and grooming.Cyclazocine: An analgesic with mixed narcotic agonist-antagonist properties.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Carboxypeptidase H: A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.Benzomorphans: Morphine derivatives of the methanobenzazocine family that act as potent analgesics.Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.D-Ala(2),MePhe(4),Met(0)-ol-enkephalin: A stable synthetic analog of methionine enkephalin (ENKEPHALIN, METHIONINE). Actions are similar to those of methionine enkephalin. Its effects can be reversed by narcotic antagonists such as naloxone.beta-Endorphin: A 31-amino acid peptide that is the C-terminal fragment of BETA-LIPOTROPIN. It acts on OPIOID RECEPTORS and is an analgesic. Its first four amino acids at the N-terminal are identical to the tetrapeptide sequence of METHIONINE ENKEPHALIN and LEUCINE ENKEPHALIN.Leucyl Aminopeptidase: A zinc containing enzyme of the hydrolase class that catalyzes the removal of the N-terminal amino acid from most L-peptides, particularly those with N-terminal leucine residues but not those with N-terminal lysine or arginine residues. This occurs in tissue cell cytosol, with high activity in the duodenum, liver, and kidney. The activity of this enzyme is commonly assayed using a leucine arylamide chromogenic substrate such as leucyl beta-naphthylamide.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Receptors, Opioid, kappa: A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the ENKEPHALINS, the DYNORPHINS, and the ENDORPHINS. Each of these families derives from different precursors, proenkephalin, prodynorphin, and PRO-OPIOMELANOCORTIN, respectively. There are also at least three classes of OPIOID RECEPTORS, but the peptide families do not map to the receptors in a simple way.Diprenorphine: A narcotic antagonist similar in action to NALOXONE. It is used to remobilize animals after ETORPHINE neuroleptanalgesia and is considered a specific antagonist to etorphine.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Etorphine: A narcotic analgesic morphinan used as a sedative in veterinary practice.Keto AcidsOligopeptides: Peptides composed of between two and twelve amino acids.Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Protein PrecursorsAnalgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Isoleucine: An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.Morphinans: Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS.Tiopronin: Sulfhydryl acylated derivative of GLYCINE.Leucine Dehydrogenase: An octameric enzyme belonging to the superfamily of amino acid dehydrogenases. Leucine dehydrogenase catalyzes the reversible oxidative deamination of L-LEUCINE, to 4-methyl-2-oxopentanoate (2-ketoisocaproate) and AMMONIA, with the corresponding reduction of the cofactor NAD+.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Adrenal Medulla: The inner portion of the adrenal gland. Derived from ECTODERM, adrenal medulla consists mainly of CHROMAFFIN CELLS that produces and stores a number of NEUROTRANSMITTERS, mainly adrenaline (EPINEPHRINE) and NOREPINEPHRINE. The activity of the adrenal medulla is regulated by the SYMPATHETIC NERVOUS SYSTEM.Kinetics: The rate dynamics in chemical or physical systems.PyrrolidinesBrain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Chromaffin Granules: Organelles in CHROMAFFIN CELLS located in the adrenal glands and various other organs. These granules are the site of the synthesis, storage, metabolism, and secretion of EPINEPHRINE and NOREPINEPHRINE.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Somatostatin: A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.Amino Acids, Branched-Chain: Amino acids which have a branched carbon chain.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Dihydromorphine: A semisynthetic analgesic used in the study of narcotic receptors.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Vas Deferens: The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Basic-Leucine Zipper Transcription Factors: A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.Injections, Intraventricular: Injections into the cerebral ventricles.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Leucine Transaminase: A PYRIDOXAL PHOSPHATE containing enzyme that catalyzes the reversible transamination of branched-chain AMINO ACIDS to 2-oxoglutarate.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Benzylidene Compounds: Compounds containing the PhCH= radical.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Myenteric Plexus: One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38)Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.Locus Coeruleus: Bluish-colored region in the superior angle of the FOURTH VENTRICLE floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the PERIAQUEDUCTAL GRAY.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Morphine Derivatives: Analogs or derivatives of morphine.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.2-Isopropylmalate Synthase: An enzyme that catalyzes the first step in the biosynthetic pathway to LEUCINE, forming isopropyl malate from acetyl-CoA and alpha-ketoisovaleric acid. This enzyme was formerly listed as EC 4.1.3.12.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs.Nociceptive Pain: Dull or sharp aching pain caused by stimulated NOCICEPTORS due to tissue injury, inflammation or diseases. It can be divided into somatic or tissue pain and VISCERAL PAIN.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Galanin: A neuropeptide of 29-30 amino acids depending on the species. Galanin is widely distributed throughout the BRAIN; SPINAL CORD; and INTESTINES. There are various subtypes of GALANIN RECEPTORS implicating roles of galanin in regulating FOOD INTAKE; pain perception; memory; and other neuroendocrine functions.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Substantia Gelatinosa: Gelatinous-appearing material in the dorsal horn of the spinal cord, consisting chiefly of Golgi type II neurons and some larger nerve cells.Electric Stimulation: Use of electric potential or currents to elicit biological responses.