Gene Symbol: Penk
Description: proenkephalin
Alias: Enk, Penk-rs, Penk1, Penk2, proenkephalin-A, enkephalin, preproenkephalin 2, proenkephalin 1, proenkephalin 2, proenkephalin related sequence
Species: rat
Products:     Penk

Top Publications

  1. Sgroi S, Capper Loup C, Paganetti P, Kaelin Lang A. Enkephalin and dynorphin neuropeptides are differently correlated with locomotor hypersensitivity and levodopa-induced dyskinesia in parkinsonian rats. Exp Neurol. 2016;280:80-8 pubmed publisher
    The opioidergic neuropeptides dynorphin (DYN) and enkephalin (ENK) and the D1 and D2 dopaminergic receptors (D1R, D2R) are involved in the striatal control of motor and behavioral function...
  2. Leibowitz S, Akabayashi A, Alexander J, Karatayev O, Chang G. Puberty onset in female rats: relationship with fat intake, ovarian steroids and the peptides, galanin and enkephalin, in the paraventricular and medial preoptic nuclei. J Neuroendocrinol. 2009;21:538-49 pubmed publisher
    ..obtained in adult rats, the present study in pubertal rats focused on the orexigenic peptides, galanin (GAL) and enkephalin (ENK), in the paraventricular nucleus (PVN) and medial preoptic nucleus (MPN), which are known to be responsive ..
  3. Yoshikawa K, Maruyama K, Aizawa T, Yamamoto A. A new species of enkephalin precursor mRNA with a distinct 5'-untranslated region in haploid germ cells. FEBS Lett. 1989;246:193-6 pubmed
    ..Biol. Chem. 259, 14301-14308; (1984) J. Biol. Chem. 259, 14309-14313]. Northern blot analysis using a 5'-end-specific probe showed that this type of preproenkephalin mRNA exists exclusively in the germ cells. ..
  4. Barson J, Fagan S, Chang G, Leibowitz S. Neurochemical heterogeneity of rats predicted by different measures to be high ethanol consumers. Alcohol Clin Exp Res. 2013;37 Suppl 1:E141-51 pubmed publisher
    ..Rats with high compared to low activity exhibited significantly greater expression of galanin and enkephalin in the paraventricular nucleus (PVN) and of orexin in the perifornical lateral hypothalamus (PFLH), but no ..
  5. Frederick A, Goldsmith J, de Zavalía N, Amir S. Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain. PLoS ONE. 2017;12:e0176279 pubmed publisher
    ..quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain...
  6. Song D, Rossier J, Harlan R. Comparison of synenkephalin and methionine enkephalin immunocytochemistry in rat brain. Peptides. 1989;10:1239-46 pubmed
    ..and distribution of synenkephalin immunoreactivity was extremely similar to that of a commercial methionine enkephalin (Met-ENK) antiserum...
  7. Chang G, Karatayev O, Barson J, Chang S, Leibowitz S. Increased enkephalin in brain of rats prone to overconsuming a fat-rich diet. Physiol Behav. 2010;101:360-9 pubmed publisher
    Recent studies have shown that the opioid enkephalin (ENK), acting in part through the hypothalamic paraventricular nucleus (PVN), can stimulate consumption of a high-fat diet...
  8. Rao S, Howells R. cis-acting elements in the 5'-untranslated region of rat testis proenkephalin mRNA regulate translation of the precursor protein. J Biol Chem. 1993;268:22164-9 pubmed
  9. Morganstern I, Liang S, Ye Z, Karatayev O, Leibowitz S. Disturbances in behavior and cortical enkephalin gene expression during the anticipation of ethanol in rats characterized as high drinkers. Alcohol. 2012;46:559-68 pubmed publisher
    ..The current investigation examined the possibility that the opioid peptide enkephalin (ENK), known to mediate some of the reinforcing properties of ethanol, may function in the mPFC during the ..

More Information


  1. Howells R, Kilpatrick D, Bhatt R, Monahan J, Poonian M, Udenfriend S. Molecular cloning and sequence determination of rat preproenkephalin cDNA: sensitive probe for studying transcriptional changes in rat tissues. Proc Natl Acad Sci U S A. 1984;81:7651-5 pubmed
    ..Like the bovine and human gene products, rat preproenkephalin contains four [Met]enkephalin sequences and one copy each of [Leu]enkephalin, [Met]enkephalin-Arg6-Gly7-Leu8, and [Met]enkephalin-Arg6-Phe7...
  2. Caffrey J, Boluyt M, Younes A, Barron B, O Neill L, Crow M, et al. Aging, cardiac proenkephalin mRNA and enkephalin peptides in the Fisher 344 rat. J Mol Cell Cardiol. 1994;26:701-11 pubmed
    Cardiac proenkephalin (PENK) mRNA, methionine-enkephalin (ME) and leucine-enkephalin (LE) were determined from 2 days of age through senescence in Fisher 344 rats...
  3. Ciriello J, Caverson M, McMurray J, Bruckschwaiger E. Co-localization of hypocretin-1 and leucine-enkephalin in hypothalamic neurons projecting to the nucleus of the solitary tract and their effect on arterial pressure. Neuroscience. 2013;250:599-613 pubmed publisher
    ..projections to cardiovascular responsive sites in the nucleus of the solitary tract (NTS) co-expressed leucine-enkephalin (L-Enk), and to determine the effects of co-administration of hcrt-1 and D-Ala2,D-Leu5-Enkephalin (DADL) into ..
  4. Chen J, Li W, Zhao X, Yang J, Xu H. [Effects of Chinese herbs on enkephalin mRNA and prodynorphin mRNA gene expression in rat hippocampus with chronic immobilization stress]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2005;21:121-5 pubmed
    To investigate the changes of enkephalin mRNA and prodynorphin mRNA gene expression in rat brain regions with chronic immobilization stress and the influence of Chinese herbs...
  5. Gao C, Niu L, Ren P, Wang W, Zhu C, Li Y, et al. Hypoxic preconditioning attenuates global cerebral ischemic injury following asphyxial cardiac arrest through regulation of delta opioid receptor system. Neuroscience. 2012;202:352-62 pubmed publisher
    ..The expression of hypoxia-inducible factor-1? (HIF-1?) and DOR, and the content of leucine enkephalin (L-ENK) in the brain were also investigated after the end of 7-day HPC...
  6. Farid W, Lawrence A, Krstew E, Tait R, Hulse G, Dunlop S. Maternally administered sustained-release naltrexone in rats affects offspring neurochemistry and behaviour in adulthood. PLoS ONE. 2012;7:e52812 pubmed publisher
    ..Collectively, these data show pronounced effects of developmental naltrexone exposure, some of which persist into adulthood, highlighting the need for follow up of humans that were exposed to naltrexone in utero. ..
  7. Just L, Olenik C, Meyer D. Neocortical projections regulate the neostriatal proenkephalin gene expression. Cereb Cortex. 1999;9:332-9 pubmed
    ..that neocortical projections to the neostriatum may regulate the neostriatal expression of the proenkephalin (PEnk) gene...
  8. Konig M, Zimmer A, Steiner H, Holmes P, Crawley J, Brownstein M, et al. Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature. 1996;383:535-8 pubmed
    ..We disrupted the pre-proenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice...
  9. Karlsson O, Kultima K, Wadensten H, Nilsson A, Roman E, Andren P, et al. Neurotoxin-induced neuropeptide perturbations in striatum of neonatal rats. J Proteome Res. 2013;12:1678-90 pubmed publisher
    ..The present study also suggests that neuropeptide profiling might provide a sensitive characterization of the BMAA-induced noncytotoxic effects on the developing brain. ..
  10. Yoshikawa K, Williams C, Sabol S. Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and distribution in the central nervous system. J Biol Chem. 1984;259:14301-8 pubmed
    ..library was constructed from poly-adenylated RNA of Fischer rat striatum and screened for inserts coding for the enkephalin precursor preproenkephalin...
  11. Rosen H, Douglass J, Herbert E. Isolation and characterization of the rat proenkephalin gene. J Biol Chem. 1984;259:14309-13 pubmed
    ..b>Enkephalin-coding sequences as well as 5' flanking sequences appear to be the most highly conserved...
  12. DiFeliceantonio A, Mabrouk O, Kennedy R, Berridge K. Enkephalin surges in dorsal neostriatum as a signal to eat. Curr Biol. 2012;22:1918-24 pubmed publisher
    ..Here, we provide evidence that enkephalin surges in an anteromedial quadrant of dorsal neostriatum contribute to generating intense consumption of ..
  13. MENDEZ M, Morales Mulia M, Pérez Luna J. Ethanol-induced changes in proenkephalin mRNA expression in the rat nigrostriatal pathway. J Mol Neurosci. 2008;34:225-34 pubmed publisher
    ..Alterations in enkephalin expression in the substantia nigra and CP in response to ethanol exposure could be involved in the mechanisms ..
  14. Llewellyn Smith I, DiCarlo S, Collins H, Keast J. Enkephalin-immunoreactive interneurons extensively innervate sympathetic preganglionic neurons regulating the pelvic viscera. J Comp Neurol. 2005;488:278-89 pubmed
    b>Enkephalin (ENK)-immunoreactive (IR) axons occur in regions containing spinal autonomic neurons and endogenous opiates contribute to spinal regulation of bladder function...
  15. Mally P, Mishra R, Gandhi S, Decastro M, Nankova B, Lagamma E. Stereospecific regulation of tyrosine hydroxylase and proenkephalin genes by short-chain fatty acids in rat PC12 cells. Pediatr Res. 2004;55:847-54 pubmed
    ..Butyrate has been shown to induce tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis, and enkephalin neuropeptide gene transcription, suggesting a role in perinatal sympathoadrenal stress-adaptation...
  16. Kilpatrick D, Zinn S, Fitzgerald M, Higuchi H, Sabol S, Meyerhardt J. Transcription of the rat and mouse proenkephalin genes is initiated at distinct sites in spermatogenic and somatic cells. Mol Cell Biol. 1990;10:3717-26 pubmed
    ..This promoter motif thus may be shared with other genes expressed in male germ cells. ..
  17. Ding Y, Tang F, Yu L, Fu Y, Zhang G, Jin G. Relevance between striatal expression of Fos, proenkephalin mRNA, prodynorphin mRNA and rotation induced by l-stepholidine in 6-hydroxydopamine-lesioned rats. Acta Pharmacol Sin. 2000;21:885-92 pubmed
    To study that l-stepholidine (SPD) regulates the expression of proenkephalin (PENK) and prodynorphin (PDYN) mRNA and Fos in the striatum after rotational test in the 6-hydroxydopamine (6-OHDA)-lesioned rats...
  18. Rosenberger J, Petrovics G, Buzas B. Oxidative stress induces proorphanin FQ and proenkephalin gene expression in astrocytes through p38- and ERK-MAP kinases and NF-kappaB. J Neurochem. 2001;79:35-44 pubmed
    ..induction of these genes by oxidative stress and these other factors may suggest a role for orphanin FQ and enkephalin in injury and stress responses of the CNS and neuropathophysiological conditions involving reactive oxygen ..
  19. Kobylecki C, Cenci M, Crossman A, Ravenscroft P. Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson's disease. J Neurochem. 2010;114:499-511 pubmed publisher
    ..These data suggest that Ca(2+)-permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti-dyskinetic therapies...
  20. Karatayev O, Barson J, Carr A, Baylan J, Chen Y, Leibowitz S. Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake. Alcohol. 2010;44:323-34 pubmed publisher
    ..ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) ..
  21. Poulin J, Laforest S, Drolet G. Enkephalin downregulation in the nucleus accumbens underlies chronic stress-induced anhedonia. Stress. 2014;17:88-96 pubmed publisher
    ..Furthermore, we observed a strong correlation between enkephalin expression and sucrose preference in the shell part of the nucleus accumbens, with a lower level of enkephalin ..
  22. Guo C, Ji B, Chen Y, Zhong D, Jin Y, Liu Q, et al. [Affection of acupotomy lysis on leu-enkephalin (L-ENK) content in different parts of centrum of rats with knee osteoarthritis]. Zhongguo Gu Shang. 2011;24:656-8 pubmed
    ..of needle-knife lysis in spinal cord and other parts of central nervous system by comparing the changes of Leu-Enkephalin (L-ENK) content in different parts of centrium of rats undergone needle-knife lysis and electro-acupuncture ..
  23. Loh Y, Maldonado A, Zhang C, Tam W, Cawley N. Mechanism of sorting proopiomelanocortin and proenkephalin to the regulated secretory pathway of neuroendocrine cells. Ann N Y Acad Sci. 2002;971:416-25 pubmed
    ..Thus, POMC and PE are sorted to the RSP at the TGN by a mechanism involving the interaction of a specific sorting signal on these molecules with the sorting receptor, CPE. ..
  24. Ragnauth A, Schuller A, Morgan M, Chan J, Ogawa S, Pintar J, et al. Female preproenkephalin-knockout mice display altered emotional responses. Proc Natl Acad Sci U S A. 2001;98:1958-63 pubmed be less active on the light side of a dark-light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments...
  25. Hildebrand B, Olenik C, Uhl A, Meyer D. Expression of the proenkephalin gene in cultured astroglial cells: analysis of cell cycle dependence. Brain Res. 1997;759:285-91 pubmed
    Glial progenitors strongly express the proenkephalin (PEnk) gene during their proliferation in the subventricular zone of the neocortex. Also in primary culture, astroglial cells from rat neocortex produce PEnk mRNA...
  26. Just L, Olenik C, Meyer D. Glial expression of the proenkephalin gene in slice cultures of the subventricular zone. J Mol Neurosci. 1998;11:57-66 pubmed
    The proenkephalin (PEnk) gene is expressed in rats in the neocortical subventricular zone (nSVZ) of the lateral ventricle during the first postnatal week, when precursors of astro- and oligoglial cells of the rat neocortex proliferate in ..
  27. Tomasiewicz H, Jacobs M, Wilkinson M, Wilson S, Nestler E, Hurd Y. Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability. Biol Psychiatry. 2012;72:803-10 pubmed publisher
    ..However, a causal link between proenkephalin (Penk) expression and vulnerability to heroin has yet to be established...
  28. Howells R. Proenkephalin biosynthesis in the rat. NIDA Res Monogr. 1986;70:43-65 pubmed
  29. Fu Z, Weihe E, Zheng Y, Schafer M, Sheng H, Corisdeo S, et al. Differential effects of rabies and borna disease viruses on immediate-early- and late-response gene expression in brain tissues. J Virol. 1993;67:6674-81 pubmed
    ..of the immediate-early-response genes (IEGs) egr-1, junB, and c-fos, and the late response gene encoding enkephalin in the brains of rats infected intranasally with Borna disease virus (BDV) or rabies virus...
  30. Alvarez Fischer D, Grundmann M, Lu L, Samans B, Fritsch B, Moller J, et al. Prolonged generalized dystonia after chronic cerebellar application of kainic acid. Brain Res. 2012;1464:82-8 pubmed publisher
  31. Cui X. [Expression and localization of immediate early genes and preproenkephalin gene in central nervous system following electroacupuncture stimulation]. Sheng Li Ke Xue Jin Zhan. 1995;26:230-2 pubmed
    ..Northern hybridization revealed that EA stimulation induced c-fos gene expression within 1-2 h, followed by PENK gene expression which peaked at 48h...
  32. Ovadia H, Magenheim Y, Behar O, Rosen H. Molecular characterization of immune derived proenkephalin mRNA and the involvement of the adrenergic system in its expression in rat lymphoid cells. J Neuroimmunol. 1996;68:77-83 pubmed
    Proenkephalin (PENK), a classically defined opioid gene, was originally thought to be expressed almost exclusively in the mature nervous and neuroendocrine systems...
  33. Engström L, Engblom D, Blomqvist A. Systemic immune challenge induces preproenkephalin gene transcription in distinct autonomic structures of the rat brain. J Comp Neurol. 2003;462:450-61 pubmed
    ..These results demonstrated that enkephalin transcription is induced in central autonomic neurons during immune challenge, suggesting that enkephalins are ..
  34. Wang Y, Nowicki M, Wang X, Arnold W, Fernandez S, Mo X, et al. Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain. Gene Ther. 2013;20:742-50 pubmed publisher
    ..We compared four different HSV1-based vectors engineered to produce one of two opioid receptor agonists (enkephalin or endomorphin), or one of two isoforms of glutamic acid decarboxylase (GAD65 or GAD67), alone and in ..
  35. Huang W, Chen J, Li Y, Lu Y, Wu X. Structures and connections of enkephalin- and ?-aminobutyric acid-immunoreactive profiles in the gustatory region of the nucleus tractus solitarius: a light and electron microscopic study. Neurol Sci. 2011;32:53-8 pubmed publisher
    GABA and enkephalin (ENK) are principle inhibitory transmitters in the rostral portion of the nucleus tractus solitarius (rNTS) for regulating the gustatory information...
  36. Chang G, Karatayev O, Barson J, Liang S, Leibowitz S. Common effects of fat, ethanol, and nicotine on enkephalin in discrete areas of the brain. Neuroscience. 2014;277:665-78 pubmed publisher
    ..of the hypothalamus (HYPO), amygdala (AMYG), and nucleus accumbens (NAc), on mRNA levels of the opioid peptide, enkephalin (ENK), using in situ hybridization and on c-Fos immunoreactivity (ir) to indicate neuronal activity, using ..
  37. Yokoyama H, Oguchi T, Goins W, Goss J, Nishizawa O, de Groat W, et al. Effects of herpes simplex virus vector-mediated enkephalin gene therapy on bladder overactivity and nociception. Hum Gene Ther. 2013;24:170-80 pubmed publisher
    We previously reported the effects of herpes simplex virus (HSV) vector-mediated enkephalin on bladder overactivity and pain...
  38. Poulin J, Berube P, Laforest S, Drolet G. Enkephalin knockdown in the central amygdala nucleus reduces unconditioned fear and anxiety. Eur J Neurosci. 2013;37:1357-67 pubmed publisher
    The endogenous opioid enkephalins (ENK) are highly expressed in the central nucleus of the amygdaloid complex (CeA) where several lines of evidence point to a potential role in the modulation of fear and anxiety...
  39. Berube P, Laforest S, Bhatnagar S, Drolet G. Enkephalin and dynorphin mRNA expression are associated with resilience or vulnerability to chronic social defeat stress. Physiol Behav. 2013;122:237-45 pubmed publisher
    ..Among the neuropeptide systems, the endogenous opioids enkephalin (ENK) and dynorphin (DYN), are very interesting candidates to participate in the naturally occurring variations ..
  40. Chang G, Barson J, Karatayev O, Chang S, Chen Y, Leibowitz S. Effect of chronic ethanol on enkephalin in the hypothalamus and extra-hypothalamic areas. Alcohol Clin Exp Res. 2010;34:761-70 pubmed publisher
    Ethanol may be consumed for reasons such as reward, anxiety reduction, or caloric content, and the opioid enkephalin (ENK) appears to be involved in many of these functions...
  41. Corchero J, Fuentes J, Manzanares J. Gender differences in proenkephalin gene expression response to delta9-tetrahydrocannabinol in the hypothalamus of the rat. J Psychopharmacol. 2002;16:283-9 pubmed
    Chronic exposure to delta9-tetrahydrocannabinol (delta9-THC) produces an activation of preproenkephalin (PENK) gene expression in the rat hypothalamus...
  42. Zhou L, Furuta T, Kaneko T. Chemical organization of projection neurons in the rat accumbens nucleus and olfactory tubercle. Neuroscience. 2003;120:783-98 pubmed
  43. Szpirer C, Szpirer J, Van Vooren P, Tissir F, Simon J, Koike G, et al. Gene-based anchoring of the rat genetic linkage and cytogenetic maps. Transplant Proc. 1999;31:1541-3 pubmed
  44. Xu N, Qiu C, Wang W, Wang Y, Chai C, Yan Y, et al. HPLC/MS/MS for quantification of two types of neurotransmitters in rat brain and application: myocardial ischemia and protection of Sheng-Mai-San. J Pharm Biomed Anal. 2011;55:101-8 pubmed publisher
    ..ranges of 10-1000ngmL(-1) for 5-hydroxytryptamine (5-HT) and norepinephrine (NE); 2-250ngmL(-1) for methionine-enkephalin (M-ENK) and leucine-enkephalin (L-ENK). Quantification limit for 5-HT and NE was 4.0ngmL(-1); and 2...
  45. Szabó F, Le W, Snyder N, Hoffman G. Comparison of the temporal programs regulating tyrosine hydroxylase and enkephalin expressions in TIDA neurons of lactating rats following pup removal and then pup return. J Mol Neurosci. 2011;45:110-8 pubmed publisher
    Dopamine (DA) and enkephalin (ENK) release from the tuberoinfundibular dopaminergic neurons (TIDA) into the hypophysial portal circulation is fundamentally different under non-lactating and lactating conditions...
  46. Rosen H, Krichevsky A, Polakiewicz R, Benzakine S, Bar Shavit Z. Developmental regulation of proenkephalin gene expression in osteoblasts. Mol Endocrinol. 1995;9:1621-31 pubmed
    Proenkephalin (PENK), a classically defined opioid gene, was originally thought to be expressed almost exclusively in the mature nervous and neuroendocrine systems...
  47. Rao S, Howells R. Molecular cloning, sequence analysis and translation of proenkephalin mRNA from rat heart. Regul Pept. 1992;40:397-408 pubmed
    ..We conclude that the scant level of proenkephalin-derived peptides in the heart is not due to an intrinsic inability of the proenkephalin transcript to translate. ..