Effects of highly potent octapeptide analogs of somatostatin on growth hormone, insulin and glucagon release

T. Karashima, R. Z. Cai, A. V. Schally

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Biological activities of highly potent octapeptide analogs of somatostatin (SS), DPhe{A figure is presented}TrpNH2 (RC-160) and DPhw{A figure is presented}TrpNH2 (RC-121), were investigated in male rats. When analog RC-1602 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 μg/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 μ/kg. In this model, RC-160 and RC-121, in doses of 30 μg/kg, induced a similar inhibition of insulin release as 200 μg/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 μg/kg. Doses of 2 and 10 μg/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.

Original languageEnglish (US)
Pages (from-to)1011-1019
Number of pages9
JournalLife Sciences
Volume41
Issue number8
DOIs
StatePublished - Aug 24 1987
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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