Effects of highly potent octapeptide analogs of somatostatin on growth hormone, insulin and glucagon release.
Biological activities of highly potent octapeptide analogs of somatostatin (SS), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), were investigated in male rats. When analog RC-160 was administered to rats in which serum growth hormone (GH) levels were elevated by pentobarbital anesthesia, a dose-related inhibition of GH was obtained at dose range of 0.1 to 2.5 micrograms/kg. The time course of GH inhibition by RC-160, RC-121 and SS-14 was studied in rats treated with phenobarbital, morphine and chlorpromazine. Analogs RC-160 and RC-121 induced a prolonged inhibition of GH levels, in contrast to SS-14, whose effect was short-lived. The analogs suppressed the GH level for more than 2 hr, the peak inhibition being seen 30 to 60 min after the injection. The effects of analogs RC-160 and RC-121 on insulin secretion were observed in rats, in which insulin levels had been elevated by intravenous administration of glucose (500 mg/rat). Administration of RC-160 suppressed insulin secretion, dose-dependently, maximum but not complete inhibition being achieved at a dose of 100 micrograms/kg. In this model, RC-160 and RC-121, in doses of 30 micrograms/kg, induced a similar inhibition of insulin release as 200 micrograms/kg of SS-14, whose action of SS-14 was transient. The effect of analog RC-160 on glucagon release was studied in rats with glucagon levels elevated by hypoglycemia. RC-160 suppressed the secretion of glucagon, the inhibition being dose-dependent in the range of 0.1 to 2 micrograms/kg. Doses of 2 and 10 micrograms/kg of this analog completely suppressed the hypoglycemia-induced glucagon release. These results indicate that analogs RC-160 and RC-121 possess prolonged and enhanced biological activities, the former analog showing a high selectivity in inhibiting GH and glucagon release in vivo as compared with that of insulin secretion.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D003864:Depression, Chemical; D005934:Glucagon / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology; D015282:Octreotide / Q000031:analogs & derivatives*; D010634:Phenobarbital / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D007328:Insulin; C051458:vapreotide; D013004:Somatostatin; D009020:Morphine; D013006:Growth Hormone; D005934:Glucagon; C053408:RC 121; D015282:Octreotide; D002746:Chlorpromazine; D010634:Phenobarbital