Brain beta-endorphin and other opioids are involved in restraint stress-induced stimulation of the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system, and the adrenal medulla in the rat.
Opiates and opioids have complex effects on the hypothalamic-pituitary-adrenal axis, and they stimulate the sympathetic nervous system. This study was designed to clarify the role of brain beta-endorphin in the mechanism by which stress increases plasma concentrations of adrenocorticotropin (ACTH), epinephrine (E), and norepinephrine (NE). Intracerebroventricular (i.c.v.) administration of beta-endorphin to rats significantly increased plasma ACTH levels at doses of 0.09, 0.3, and 1.5 nmol, and plasma E and NE levels at doses of 0.3 and 1.5 nmol. The rise of plasma ACTH, E, and NE levels by 0.3 nmol beta-endorphin was inhibited by intravenous (i.v.) administration of 2 mg/kg b.wt. naloxone. I.v. administration of anti-rat corticotropin-releasing hormone (CRH) rabbit serum completely blocked the beta-endorphin-induced ACTH secretion without affecting the secretion of E and NE. I.c.v. administration of anti-beta-endorphin rabbit gamma-globulin attenuated a 30-min restraint stress-induced rise of plasma ACTH levels without significant influence on the rise of E and NE levels, whereas i.v. administration of naloxone attenuated the restraint stress-induced rise of plasma ACTH, E and NE levels. These results suggest that i.c.v. administration of beta-endorphin stimulates the secretion of ACTH, E, and NE through opiate receptor, and that brain CRH mediates the beta-endorphin-induced secretion of ACTH. The results also suggest that brain beta-endorphin is, at least in part, involved in the restraint stress-induced stimulation of the hypothalamic-pituitary-adrenal axis, and that some opioids other than beta-endorphin are involved in the stimulatory mechanism of the autonomic nervous system and the adrenal medulla in the rat.
Yamauchi
N
N
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Japan.
Shibasaki
T
T
Wakabayashi
I
I
Demura
H
H
D000313:Adrenal Medulla / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D018847:Opioid Peptides / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D001615:beta-Endorphin / Q000276:immunology / Q000378:metabolism*; D005719:gamma-Globulins / Q000494:pharmacology
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D005719:gamma-Globulins; D009270:Naloxone; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine; D004837:Epinephrine