Central opiate modulation of growth hormone and insulin-like growth factor-I.
The effects of central administration of morphine-sulfate (MOR:80 micrograms) and morphine-6-glucuronide (M6G:1 microgram) on the growth hormone (GH)/insulin-like growth factor (IGF) system were assessed. MOR and M6G were injected intracerebroventricularly (ICV) in chronically catheterized 24 h fasted rats; time-matched control animals received H2O (5 microliters). MOR increased plasma GH concentrations 3-fold 2 h after i.c.v. injection, and transiently increased the plasma concentration and liver content of IGF-I (60% and 90%, respectively) 30 min after i.c.v injection. M6G did not produce any significant alterations in plasma GH and IGF-I levels at the time-points measured. Both MOR and M6G increased the concentration of IGF binding protein-1 (IGFBP-1) in plasma and liver 2 h after injection. However, MOR showed 2- to 2.5-fold greater effect than M6G in stimulating plasma and liver IGFBP-1. MOR and M6G produced similar increases in plasma epinephrine (5-fold), norepinephrine (3-fold) and corticosterone (1.5-fold). Neither opiate significantly altered circulating insulin levels. These findings suggest that opiate modulation of GH and IGF may be hormone-independent and centrally modulated. We speculate that differential affinities of MOR and M6G to the different opiate receptor subtypes might be responsible for their distinct effects on GH/IGF-I system.
Hashiguchi
Y
Y
Department of Surgery, SUNY at Stony Brook 11794-8191, USA.
Molina
P E
PE
Fan
J
J
Lang
C H
CH
Abumrad
N N
NN
D000818:Animals; D001786:Blood Glucose; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000737:chemistry; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D007334:Insulin-Like Growth Factor I; D009020:Morphine; D013006:Growth Hormone; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine