PMID- 11250660 OWN - NLM STAT- MEDLINE DCOM- 20010426 LR - 20190709 IS - 0022-0795 (Print) IS - 0022-0795 (Linking) VI - 169 IP - 1 DP - 2001 Apr TI - Endomorphins and activation of the hypothalamo-pituitary-adrenal axis. PG - 185-93 AB - Endomorphin (EM)-1 and EM-2 are opioid tetrapeptides recently located in the central nervous system and immune tissues with high selectivity and affinity for the mu-opioid receptor. Intracerebroventricular (i.c.v.) administration of morphine stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The present study investigated the effect of centrally administered EM-1 and EM-2 on HPA axis activation. Rats received a single i.c.v. injection of either EM-1 (0.1, 1.0, 10 microg), EM-2 (10 microg), morphine (10 microg), or vehicle (0.9% saline). Blood samples for plasma corticosterone determinations were taken immediately prior to i.c.v. administration and at various time points up to 4 h post-injection. Trunk blood, brains and pituitaries were collected at 4 h. Intracerebroventricular morphine increased plasma corticosterone levels within 30 min, whereas EM-1 and EM-2 were without effect. In addition, pre-treatment of i.c.v. EM-1 did not block the rise in corticosterone after morphine. Corticotrophin-releasing factor (CRF) mRNA and arginine vasopressin (AVP) mRNA in the paraventricular nucleus (PVN) and POMC mRNA in the anterior pituitary were found to be unaffected by either morphine or endomorphins. Since release of other opioids are elevated in response to acute stress, we exposed rats to a range of stressors to determine whether plasma EM-1 and EM-2 can be stimulated by HPA axis activation. Plasma corticosterone, ACTH and beta-endorphin were elevated following acute restraint stress, but concentrations of plasma EM-1-immunoreactivity (ir) and EM-2-ir did not change significantly. Corticosterone, ACTH and beta-endorphin were further elevated in adjuvant-induced arthritis (AA) rats by a single injection of lipopolysaccharide (LPS), but not by restraint stress. In conclusion, neither EM-1 or EM-2 appear to influence the regulation of the HPA axis. These data suggest that endomorphins may be acting on a different subset of the mu-opioid receptor than morphine. The failure to induce changes in plasma EM-ir in response to the chronic inflammatory stress of AA, the acute immunological stress of LPS, or the psychological stress of restraint, argues against an important role for endomorphins in mediating HPA axis activity. FAU - Coventry, T L AU - Coventry TL AD - University Research Centre for Neuroendocrinology, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK. FAU - Jessop, D S AU - Jessop DS FAU - Finn, D P AU - Finn DP FAU - Crabb, M D AU - Crabb MD FAU - Kinoshita, H AU - Kinoshita H FAU - Harbuz, M S AU - Harbuz MS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Lipopolysaccharides) RN - 0 (Oligopeptides) RN - 0 (Receptors, Opioid, mu) RN - 0 (endomorphin 1) RN - 3PH5M0466G (endomorphin 2) RN - 60617-12-1 (beta-Endorphin) RN - 76I7G6D29C (Morphine) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - W980KJ009P (Corticosterone) SB - IM MH - Adrenocorticotropic Hormone/blood MH - Analysis of Variance MH - Animals MH - Arthritis, Reactive/blood MH - Chromatography, High Pressure Liquid MH - Corticosterone/blood MH - Hypothalamo-Hypophyseal System/*drug effects/metabolism MH - In Situ Hybridization/methods MH - Lipopolysaccharides/pharmacology MH - Male MH - Morphine MH - Oligopeptides/blood/*pharmacology MH - Pituitary-Adrenal System/*drug effects/metabolism MH - Radioimmunoassay/methods MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Opioid, mu/*agonists MH - Stimulation, Chemical MH - Stress, Psychological MH - beta-Endorphin/blood EDAT- 2001/03/16 10:00 MHDA- 2001/05/01 10:01 CRDT- 2001/03/16 10:00 PHST- 2001/03/16 10:00 [pubmed] PHST- 2001/05/01 10:01 [medline] PHST- 2001/03/16 10:00 [entrez] AID - JOE03894 [pii] AID - 10.1677/joe.0.1690185 [doi] PST - ppublish SO - J Endocrinol. 2001 Apr;169(1):185-93. doi: 10.1677/joe.0.1690185.