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Abstract
Background. Somatostatin analogues inhibit peptide release and cell growth through multiple postreceptor
signal transduction mechanisms (PRSTM), including G proteins (GP), cyclic adenosine
monophosphate (cAMP), calcium, protein kinase C (PKC), and tyrosine phosphatase (TP).
Octreotide acetate (OA), a somatostatin analogue, has been shown to inhibit angiogenesis;
however, the PRSTM involved are unknown.
Methods. Fertilized chicken eggs were obtained and incubated. On day 3, embryos were removed
and placed in plastic wrap hammocks. On day 7, disks containing OA, test substances
that interfere with PRSTM, or combinations of OA plus a. test substance were placed
on the developing chorioallantoic membrane. Blood vessel growth under each disk was
assessed at 24 hours. Data were evaluated by chi-squared analysis.
Results. OA's ability to inhibit angiogenesis is significantly diminished when combined with
calcium, bradykinin (increases calcium), pertussis toxin (inhibits GP), or 3-isobutyl-1
methylxanthine (increases cAMP). In contrast, no significant decrease is noted in
OA's ability to inhibit angiogenesis when combined with phorbol ester (activates PKC)
or vanadale (inhibits TP).
Conclusions. OA-induced inhibition of angiogenesis is GP, calcium, and cAMP dependent and is PKC
and TP independent. Better understanding of the PRSTM involved with OA-induced inhibition
of angiogenesis may lead to enhancement of OA's effect on angiogenesis.
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References
- Inhibition of gastrin and gastric acid secretion by growth-hormone release inhibiting hormone.Lancet. 1974; 2: 1106-1109
- Inhibition by somatostatin of glucagon and insulin release from perfused rat pancreas in response to arginine, isoproterenol and theophylline: evidence for a preferential effect on glucagon secretion.Endocrinology. 1975; 96: 749-754
- Role of vasoactive intestinal polypeptide (VIP) and endogenous somatostatin on the secretion of epidermal growth factor (EGF): studies on duodenal tissue cultures.Regul Pept. 1990; 29: 75-80
- Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase.in: Proc Natl Acad Sci. 86. 1989: 2003-2007
- Inhibitory effects of somatostatin on rat hepatocyte proliferation are mediated by cyclic AMP.J Surg Res. 1991; 51: 113-118
- Direct inhibitory effects of somatostatin (analogues) on the growth of human breast cancer cells.Cancer Res. 1987; 47: 1566-1570
- Cyclic AMP-Independent, dual regulation of voltage-dependent Ca++ currents by CHRH and somatostatin in a pituitary cell line.EMBO J. 1988; 6: 1627-1633
- Somatostatin inhibits multireceptor stimulation of cyclic AMP formation and corticotropin secretion in mouse pituitary tumor cells.in: Proc Natl Acad Sci. 79. 1982: 6502-6506
- Protein kinase-C is not essential for growth hormone (GH)-releasing factor-induced GH release from rat somatotrophs.Endocrinology. 1989; 124: 2235-2344
- Multiple mechanisms of somatostatin inhibition of adrenocorticotropin release from mouse anterior pituitary cells.Endocrinology. 1985; 116: 2259-2266
- Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane.J Surg Res. 1991; 50: 245-251
- Effects of varying chamber construction and embryo pre-incubation age on survival and growth of chick embryos in shell-less culture.Anat Rec. 1981; 199: 33-43
- Angiogenesis: initiation and control.Ann N Y Acad Sci. 1982; 401: 212-226
- A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment.Science. 1985; 230: 1375-1378
- Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent.J Surg Res. 1993; 55: 446-450
- Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides.Mol Pharmacol. 1993; 43: 838-844
- Characterization of cloned somatostatin receptors SSTR4 and SSTR4.Mol Pharmacol. 1993; 44: 385-392
- Inhibitory effect of somatostatin on CAMP accumulation and calcitonin secretion in C-cells: involvement of pertussis toxin-sensitive G-proteins.Mol Cell Endocrinol. 1992; 86: 213-219
- Somatostatin inhibits insulin secretion by a G-protein-mediated decrease in Ca2+ entry through voltage-dependent Ca2+ channels in the beta cell.J Biol Chem. 1991; 266: 837-843
- Evidence that receptor-linked G-protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells.J Neurochem. 1990; 54: 30-33
- Guanine nucleotides induce Ca2+-independent insulin secretion from permeabilized RINm5F cells.J Biol Chem. 1987; 262: 5049-5065
- Suppression of insulin release by galanin and somatostatin is mediated by a G-protein.J Biol Chem. 1989; 264: 973-980
- Oscillations of cytosolic Ca2+ in pituitary cells due to action potentials.Nature. 1987; 329: 719-721
- Electrophysiological responses of rat pituitary cells in somatotroph-enriched primary culture to human growth-hormone releasing factor.Neuroendocrinology. 1989; 50: 679-687
- G-protein activation of a hormone-stimulated phosphatase in human tumor cells.Science. 1992; 256: 1215-1217
Article info
Footnotes
☆Presented at the Fifteenth Annual Meeting of the American Association of Endocrine Surgeons, Dearborn, Mich., April 17–19, 1994.
Identification
Copyright
© 1994 Published by Elsevier Inc.