Corticotropin-releasing factor (CRF) receptor-1 is involved in cardiac noradrenergic activity observed during naloxone-precipitated morphine withdrawal.

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Disease Models, Animal*; Adrenergic Neurons/*metabolism ; Corticotropin-Releasing Hormone/*metabolism ; Heart Ventricles/*innervation ; Morphine Dependence/*metabolism ; Receptors, Corticotropin-Releasing Hormone/*metabolism; Animals ; HSP27 Heat-Shock Proteins/metabolism ; Heart Ventricles/metabolism ; Heart Ventricles/physiopathology ; Hypertension/etiology ; Hypothalamo-Hypophyseal System/metabolism ; Hypothalamo-Hypophyseal System/physiopathology ; Male ; Mice ; Mice, 129 Strain ; Mice, Knockout ; Morphine Dependence/physiopathology ; Naloxone ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Phosphorylation ; Pituitary-Adrenal System/metabolism ; Pituitary-Adrenal System/physiopathology ; Protein Processing, Post-Translational ; Receptors, Corticotropin-Releasing Hormone/genetics ; Signal Transduction ; Tachycardia/etiology ; CRF Receptor, Type 1

Background and Purpose: The negative affective states of withdrawal involve the recruitment of brain and peripheral stress circuitry [noradrenergic activity, induction of the hypothalamic-pituitary-adrenocortical (HPA) axis and activation of heat shock proteins (Hsps)]. Corticotropin-releasing factor (CRF) pathways are important mediators in the negative symptoms of opioid withdrawal. We performed a series of experiments to characterize the role of the CRF₁ receptor in the response of stress systems to morphine withdrawal and its effect in the heart using genetically engineered mice lacking functional CRF₁ receptors.
Experimental Approach: Wild-type and CRF₁ receptor-knockout mice were treated with increasing doses of morphine. Precipitated withdrawal was induced by naloxone. Plasma adrenocorticotropic hormone (ACTH) and corticosterone levels, the expression of myocardial Hsp27, Hsp27 phosphorylated at Ser⁸², membrane (MB)- COMT, soluble (S)-COMT protein and NA turnover were evaluated by RIA, immunoblotting and HPLC.
Key Results: During morphine withdrawal we observed an enhancement of NA turnover in parallel with an increase in mean arterial blood pressure (MAP) and heart rate (HR) in wild-type mice. In addition, naloxone-precipitated morphine withdrawal induced an activation of HPA axis and Hsp27. The principal finding of the present study was that plasma ACTH and corticosterone levels, MB-COMT, S-COMT, NA turnover, and Hsp27 expression and activation observed during morphine withdrawal were significantly inhibited in the CRF₁ receptor-knockout mice.
Conclusion and Implications: Our results demonstrate that CRF/CRF₁ receptor activation may contribute to stress-induced cardiovascular dysfunction after naloxone-precipitated morphine withdrawal and suggest that CRF/CRF₁ receptor pathways could contribute to cardiovascular disease associated with opioid addiction.
(© 2013 The British Pharmacological Society.)

Pharmacol Biochem Behav. 2011 Mar;98(1):28-34. (PMID: 21147152)
J Cardiovasc Pharmacol. 2002 Sep;40(3):363-9. (PMID: 12198322)
Pharmacol Ther. 2002 Jan;93(1):51-75. (PMID: 11916541)
J Pharmacol Exp Ther. 2012 Sep;342(3):665-75. (PMID: 22647273)
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18649-54. (PMID: 16339307)
Peptides. 1992 Jan-Feb;13(1):1-6. (PMID: 1320258)
J Biol Chem. 1992 Apr 15;267(11):7718-25. (PMID: 1560006)
Cell Biochem Biophys. 2011 Nov;61(2):303-11. (PMID: 21626435)
CNS Neurol Disord Drug Targets. 2012 May;11(3):306-23. (PMID: 22483300)
J Mol Cell Cardiol. 2011 Jul;51(1):129-39. (PMID: 21530534)
Brain Res Brain Res Rev. 1997 Sep 19;24(2-3):115-95. (PMID: 9385454)
J Forensic Sci. 2011 May;56(3):645-8. (PMID: 21361943)
Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1108-12. (PMID: 7755719)
Am J Psychiatry. 2007 Aug;164(8):1149-59. (PMID: 17671276)
Eur J Neurosci. 2000 Dec;12(12):4398-404. (PMID: 11122350)
Regul Pept. 2004 Jun 15;119(1-2):53-9. (PMID: 15093697)
Basic Res Cardiol. 2011 May;106(3):473-83. (PMID: 21287352)
Neuropsychopharmacology. 2006 Mar;31(3):675-84. (PMID: 16395295)
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3113-23. (PMID: 18653439)
Mol Cell Endocrinol. 2010 Aug 30;325(1-2):1-7. (PMID: 20416357)
J Comp Neurol. 1998 Nov 30;401(4):480-505. (PMID: 9826274)
Mol Psychiatry. 2002;7(9):967-74. (PMID: 12399950)
Trends Endocrinol Metab. 2008 Jul;19(5):175-80. (PMID: 18394919)
Mol Pharmacol. 2010 May;77(5):864-73. (PMID: 20159948)
Forensic Sci Int. 2009 May 30;187(1-3):42-6. (PMID: 19304418)
Neuropeptides. 2003 Dec;37(6):362-8. (PMID: 14698679)
PLoS One. 2012;7(10):e47167. (PMID: 23056601)
J Neurochem. 2010 Jul;114(2):475-87. (PMID: 20438612)
J Neurochem. 2000 Jan;74(1):199-208. (PMID: 10617121)
Neuron. 2008 Jul 10;59(1):11-34. (PMID: 18614026)
J Physiol. 1993 Jan;460:221-9. (PMID: 8487193)
Neuropsychopharmacology. 2000 Apr;22(4):388-99. (PMID: 10700658)
J Mol Cell Cardiol. 2010 Sep;49(3):370-9. (PMID: 20600103)
Behav Brain Res. 2007 Jan 25;176(2):251-8. (PMID: 17123639)
Annu Rev Pharmacol Toxicol. 2004;44:525-57. (PMID: 14744257)
Br J Pharmacol. 2010 Aug;160(7):1577-9. (PMID: 20649561)
Eur J Pharmacol. 2010 Apr 25;632(1-3):1-6. (PMID: 20132811)
Heart. 2011 Dec;97(24):2056-62. (PMID: 21690608)
Eur J Pharmacol. 2003 May 23;469(1-3):111-5. (PMID: 12782192)
Heart Dis. 2003 Jul-Aug;5(4):253-71. (PMID: 12877759)
Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1746-53. (PMID: 16731654)
Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):120-4. (PMID: 15274053)
Pharmacol Rev. 2012 Oct;64(4):901-38. (PMID: 23023031)
Psychopharmacology (Berl). 2012 Mar;220(2):379-93. (PMID: 21947312)
Psychopharmacology (Berl). 2011 Apr;214(4):779-89. (PMID: 21088959)
Br J Pharmacol. 2010 Aug;160(7):1573-6. (PMID: 20649560)
Neuron. 2007 Feb 15;53(4):577-89. (PMID: 17296558)
Psychoneuroendocrinology. 1995;20(8):789-819. (PMID: 8834089)
Br J Pharmacol. 2008 Sep;155(1):73-83. (PMID: 18536752)
Br J Pharmacol. 2013 Dec;170(8):1449-58. (PMID: 24528237)
Drug Discov Ther. 2011 Apr;5(2):71-5. (PMID: 22466143)
Circulation. 2001 Feb 13;103(6):850-5. (PMID: 11171794)
Am J Physiol Gastrointest Liver Physiol. 2002 May;282(5):G894-903. (PMID: 11960785)
J Comp Neurol. 1982 Mar 1;205(3):260-72. (PMID: 6122696)
Biol Psychiatry. 2009 Jul 15;66(2):110-7. (PMID: 19217073)
Heart. 2011 Dec;97(24):1995-6. (PMID: 21880648)
Brain Res. 2010 Feb 16;1314:3-14. (PMID: 19912996)
J Neurosci. 2007 Feb 21;27(8):2025-34. (PMID: 17314298)
ARYA Atheroscler. 2011 Fall;7(3):111-7. (PMID: 22577457)
Brain Res. 2006 Feb 9;1072(1):46-54. (PMID: 16423327)
Life Sci. 2006 Apr 25;78(22):2543-9. (PMID: 16325209)
Psychopharmacology (Berl). 2012 Jul;222(2):325-36. (PMID: 22322324)

Keywords: CRF1 receptor knockout mice; Hsp 27; NA turnover; heart; naloxone-precipitated morphine withdrawal

0 (HSP27 Heat-Shock Proteins)
0 (Hspb2 protein, mouse)
0 (Nerve Tissue Proteins)
0 (Receptors, Corticotropin-Releasing Hormone)
36B82AMQ7N (Naloxone)
5CLY6W2H1M (CRF Receptor, Type 1)
9015-71-8 (Corticotropin-Releasing Hormone)

Date Created: 20140205 Date Completed: 20141007 Latest Revision: 20250103

20250114

PMC3969081

10.1111/bph.12511

24490859