TY - JOUR
T1 - Effects of highly potent octapeptide analogs of somatostatin on growth hormone, insulin and glucagon release
AU - Karashima, T.
AU - Cai, R. Z.
AU - Schally, A. V.
N1 - Funding Information:
The work described in this paper was supported by the National Institutes of Health Grants DK07467 and CA 40077 (to A.V.S.) and by the Medical Research Service of the Veterans Administration. We thank the National Hormone and Pituitary Program (NHPP) for the gifts of materials used in RIA. The participation of Dr. R. Lu in earlier phases of this project is acknowledged. We also thank Miss Martha Sampson, Dr. J.l. Paz and Mr. Weldon Carter for their valuable experimental assistance.
PY - 1987/8/24
Y1 - 1987/8/24
N2 - 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.
AB - 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.
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U2 - 10.1016/0024-3205(87)90690-4
DO - 10.1016/0024-3205(87)90690-4
M3 - Article
C2 - 2886886
AN - SCOPUS:0023214645
VL - 41
SP - 1011
EP - 1019
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 8
ER -