Inhibition by six somatostatin analogs of plasma growth hormone levels stimulated by thiamylal and morphine in the rat.
Administration of sodium thiamylal (50 mg/kg,i.p.) and morphine (3 mg/animal,s.c.) leads to high plasma levels of growth hormone (GH) with a maximum measured approximately 30 min after injection. When the same dose of morphine is administered 60 and 120 min later and small additional doses of thiamylal are injected to maintain the animals deeply anesthetized, constant high levels of plasma GH are maintained up to the last interval studied (3 h). This in vivo model has been used to evaluate the potency and duration of action of somatostatin and of six of its analogs by serial blood sampling of animals bearing a cannula inserted into the right superior vena cava. A significant inhibitory effect of somatostatin (45% inhibition) is observed 15 min after a s.c. injection of 1 mug of the peptide while a near maximal effect (90-95% inhibition) is found at a dose of 25 mug. Both the degree of inhibition and duration of action of somatostatin are dose-dependent. Inhibitory activities equivalent to 1-250 mug of somatostatin can be measured with the model described. [Tyr1] somatostatin, [D-Ala1]somatostatin, [N-acetyl-Cys3] somatostatin and [N-benzoyl-Cys3] somatostatin have activities indistinguishable from somatostatin itself while [D-Lys4] somatostatin and [des-amino1, des-carboxy14] somatostatin have approximately 10% the activity of the natural hypothalamic peptide. This in vivo model offers advantageous characteristics of precision and reproducibility for the evaluation of potency of inhibitors of GH release.
D000818:Animals; D013006:Growth Hormone / Q000097:blood*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013840:Thiamylal / Q000494:pharmacology*; D013997:Time Factors
D013840:Thiamylal; D013004:Somatostatin; D009020:Morphine; D013006:Growth Hormone