Reevaluation of the role of alpha 2-adrenoreceptors in morphine-stimulated release of growth hormone.
The relationship between opioidergic and alpha 2-adrenergic system in the regulation of GH secretion was studied using a novel alpha 2-antagonist, CH-38083, and chronic treatment with yohimbine or clonidine. In male Wistar rats morphine (3 mg/kg s.c.), and clonidine (31 micrograms/kg i.p.) induced a significant increase in plasma GH levels. The pretreatment with the alpha 2-antagonist yohimbine (1 and 3 mg/kg) effectively inhibited the GH releasing effect or morphine and clonidine. CH-38083 at the dose of 1 mg/kg did not interfere with the morphine-induced GH secretion, while it fully antagonized the GH-releasing effect of clonidine. Higher doses (3 and 5 mg/kg) of CH-38083 only partly inhibited GH secretion induced by morphine. In rats chronically treated with clonidine (2 micrograms/ml in the drinking water for 14 days) the GH response to an injection of clonidine was blocked, while the effect of morphine on the GH secretion remained unchanged. In long-term castrated rats the effect of clonidine (15, 31 and 250 micrograms/kg i.p.) on the GH secretion was significantly blunted, while the GH-releasing effect of morphine (1, 3 and 5 mg/kg s.c.) remained unchanged. The replacement of testosterone (10 mg/kg for 4 days) in castrates restored the effect of clonidine, whereas it decreased the stimulatory action of morphine on the GH secretion. In rats chronically treated with yohimbine (2 mg/kg i.p. 2-3 times daily for 14 days until sacrifice), the GH response to a high dose of clonidine (0.5 mg/kg i.p.) was blocked, while the effect of morphine (5 mg/kg s.c.) was significantly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
D T
DT
Kiem
L
L
Bartha
L G
LG
Hársing
G B
GB
Makara
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D001599:Berberine; C048886:7,8-(methylenedioxy)-14-hydroxyberbane; D015016:Yohimbine; D013739:Testosterone; D009020:Morphine; D013006:Growth Hormone; D003000:Clonidine