Of enkephalins

Several peptides are related in different ways to these classical opioid peptides. FMREamide (Phe-Met-Arg-Phe-NH2) contains the first four amino acids of enkephalin and is active in various invertebrates (58) FMREamide-related peptides also have been located in the mammalian brain. Although these... 

Neurotensin. This hormone has been isolated and characterized from acid—acetone extracts of bovine hypothalamus (118) on the basis of its hypotensive activity. Immunoreactive neurotensin is present in mammalian gut and is distributed throughout the central nervous system its highest concentration is in the hypothalamus and in the substantia gelatinosa of the spinal cord (119). Its overall brain distribution is not unlike that of enkephalin ( ) ... 

Cytotoxics cause an elevation of dopamine levels in the area postrema in animal studies and may release prostaglandins and inhibit enzymes such as enkepha-linases to allow increased levels of enkephalins to activate opioid receptors on dopaminergic nerves. 

Using liposomes made from phospholipids as models of membrane barriers, Chakrabarti and Deamer [417] characterized the permeabilities of several amino acids and simple ions. Phosphate, sodium and potassium ions displayed effective permeabilities 0.1-1.0 x 10 12 cm/s. Hydrophilic amino acids permeated membranes with coefficients 5.1-5.7 x 10 12 cm/s. More lipophilic amino acids indicated values of 250 -10 x 10-12 cm/s. The investigators proposed that the extremely low permeability rates observed for the polar molecules must be controlled by bilayer fluctuations and transient defects, rather than normal partitioning behavior and Born energy barriers. More recently, similar magnitude values of permeabilities were measured for a series of enkephalin peptides [418]. 

Figure 8.2 The endogenous analgesic system. The three major components of the endogenous analgesic system include the periaqueductal gray matter in the midbrain nucleus raphe magnus in the medulla and pain inhibitory complex in the dorsal horns of the spinal cord. This system causes presynaptic inhibition of pain fibers entering the spinal cord. The binding of enkephalin to opioid receptors on the pain fibers prevents release of the neurotransmitter, substance P. As a result, the pain signal is terminated in the spinal cord and does not ascend to higher centers in the CNS.

Rasmussen, G. J., Bundgaard, H., Prodrugs of peptides 15. 4-Imida-zolidinone prodrug derivatives of enkephalines to prevent aminopep-tidase-catalyzed metabolism in plasma and absorptive mucosae, Int. J. 

Lakowicz et al.(]7] VB) examined the intensity and anisotropy decays of the tyrosine fluorescence of oxytocin at pH 7 and 25 °C. They found that the fluorescence decay was best fit by a triple exponential having time constants of 80, 359, and 927 ps with respective amplitudes of 0.29, 0.27, and 0.43. It is difficult to compare these results with those of Ross et al,(68) because of the differences in pH (3 vs. 7) and temperature (5° vs. 25 °C). For example, whereas at pH 3 the amino terminus of oxytocin is fully protonated, at pH 7 it is partially ionized, and since the tyrosine is adjacent to the amino terminal residue, the state of ionization could affect the tyrosine emission. The anisotropy decay at 25 °C was well fit by a double exponential with rotational correlation times of 454 and 29 ps. Following the assumptions described previously for the anisotropy decay of enkephalin, the longer correlation time was ascribed to the overall rotational motion of oxytocin, and the shorter correlation time was ascribed to torsional motion of the tyrosine side chain. 

G. J. Rasmussen, H. Bundgaard, Prodrugs of Peptides. 15. 4-hnidazolidinone Prodrug Derivatives of Enkephalins to Prevent Aminopeptidase-Catalyzed Metabohsm in Plasma and Absorptive Mucosa , Int. J. Pharm. 1991, 76, 113- 122. 

Hine B. (1985). Morphine and delta 9-tetrahydrocannabinol two-way cross tolerance for antinociceptive and heart-rate responses in the rat. Psychopharmacology (Berlin). 87(1) 34-38. HokfeItT, Elde R, Johansson 0, Terenuis L, Stein L. (1977). The distribution of enkephalin-immunoreactive cell bodies in the rat central nervous system. Neurosci Lett. 5 25. 

Sar M, Stumpf WE, Miller RJ, Chang KJ, Cuatrecasas P. (1978). Immunohisto-chemical localization of enkephalin in the rat brain and spinal cord. J Comp Neurol. 182 17-37. 

Lorenz SA, Moy MA, Dolan AR, Wood TD. 1999. Electrospray ionization fourier transform mass spectrometry quantification of enkephalin using an internal standard. Rapid Commun Mass Spectrom 13 2098. 

C]glycine] methionine enkephalin by varying the lipid concentration in the presence of a 1.2 mg/ml sample of enkephalin Figures 7 and 8 represent plots of(Ti p/T p-Tj... 

The present study has shown that enkephalin binds to PS in a pH-dependent fashion. The binding most likely involves the NHa group of the tyrosine residue of enkephalin and the CO2 group of PS. We have measured for the interaction and find it to be of the order of 5 x 10 M ("pH" 6.3) which is much weaker than the interaction of PS with morphine derivatives. Upon binding of enkephalin to PS the correlation time for internal motion in the backbone of the peptide increases by at least one order of magnitude (from 7.0 x 10" sec rad" ). The Ti of the bound peptide... 

We believe this study to be preliminary to the full mapping of the enkephalin interaction with PS and to the investigation of enkephalin in high affinity binding. Future studies should involve [4-[2- C]phenylalanine]methionine enkephalin and [2,.[2- C]glycine]methionine enkephalinamide, which are in preparation. These studies will allow more accurate determination of the rates of overall and internal motion in enkephalin and help elucidate further the nature of enkephalin-lipid interactions. ... 

In the hippocampus, enkephalins facilitate and dynorphins inhibit longterm potentiation (Simmons and Chavkin, 1996). Consistent with the role of these peptides in nociception, electroacupuncture selectively induces release of enkephalins and dynorphins in both human and experimental animals (Ulett et al., 1998). 

Table II. Receptor Blading Affinities of Enkephalin Analogs for [ H]-Labelled Naloxone ([ HJNAL) and [ H)-Labelled CD Ala, D-Leu lEnkephalln (I HlDAPLE) In Rat Brain Homogenates ...

Rigid Geometry Studies of Enkephalin The enkephalins are linear pentapeptides, H-Tyr-Gly-Gly-Phe-Met-NH2 (see Figure 2a.) and H-Tyr-Gly-Gly-Phe-Leu-NH2, which bind to several classes of opiate receptors in the mammalian brain including the same receptor as morphine(26,27). Enkephalins have drawn the interest of theoretical biophysicists for two reasons. First, because of their natural opiate activity, it is hoped that improved analgesics can be developed. Second, as pentapeptides, enkephalins are small enough that the molecule can be examined theoretically without excessive expense of computer time. 

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