Clonidine potentiates the growth hormone (GH) response to GH-releasing hormone in norepinephrine synthesis-inhibited rats: evidence for an alpha-2-adrenergic control of hypothalamic release of somatostatin.
The aim of this study was to investigate whether central alpha 2-adrenergic pathways act, in rats, by inhibiting somatostatin (SS) release, as it has been postulated to occur in other species. The growth hormone (GH) responses to GH-releasing hormone (GRF, 3 micrograms/kg i.v.) or clonidine (CLO, 100 micrograms/kg, i.v.), either given alone or in combination, were tested in male rats in which norepinephrine synthesis had been previously blocked with the dopamine-beta-hydroxylase inhibitor diethyldithio-carbamate (DDTC, 400 mg/kg i.p.). These experiments were also carried out in a control group of animals that had been given placebo (P) instead of DDTC. The GH responses to GRF in the presence of anti-SS serum given to other P and DDTC rats, allowed us to assess whether DDTC treatment had induced increased SS secretion. GH tests were carried out during spontaneous (P) or pharmacologically induced (DDTC) trough periods. Therefore, the mean (+/- SEM) GRF-induced GH peak was similarly low in both groups of rats (P: 66.5 +/- 16.6 micrograms/l; DDTC: 58 +/- 14 micrograms/l). The administration of anti-SS serum significantly (p < 0.01) increased these responses (P: 413 +/- 22; DDTC: 695 +/- 36; p < 0.01 vs. P). CLO administration elicited a maximal GH peak significantly higher (p < 0.05) in P (20.5 +/- 3) than in DDTC rats (4.1 +/- 2); however, the former was significantly lower than GH responses to GRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Lima
L
L
Department of Physiology, Faculty of Medicine, University of Santiago de Compostela, Spain.
Arce
V
V
Tresguerres
J A
JA
Devesa
J
J
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology; D004357:Drug Synergism; D013006:Growth Hormone / Q000097:blood* / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism*
D018341:Receptors, Adrenergic, alpha-2; D013004:Somatostatin; D013006:Growth Hormone; D004050:Ditiocarb; D003000:Clonidine; D009638:Norepinephrine