Advertisement
Research Article| Volume 116, ISSUE 6, P1148-1152, December 1994

Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis

  • Pranay C. Patel
    Affiliations
    From the Department of Surgery, Section of Surgical Endocrinology, Louisiana State University, New Orleans, La., USA

    Department of Surgery, Oregon Health Sciences University, Portland, Ore., USA
    Search for articles by this author
  • Rosemary Barrie
    Affiliations
    From the Department of Surgery, Section of Surgical Endocrinology, Louisiana State University, New Orleans, La., USA

    Department of Surgery, Oregon Health Sciences University, Portland, Ore., USA
    Search for articles by this author
  • Nancy Hill
    Affiliations
    From the Department of Surgery, Section of Surgical Endocrinology, Louisiana State University, New Orleans, La., USA

    Department of Surgery, Oregon Health Sciences University, Portland, Ore., USA
    Search for articles by this author
  • Scott Landeck
    Affiliations
    From the Department of Surgery, Section of Surgical Endocrinology, Louisiana State University, New Orleans, La., USA

    Department of Surgery, Oregon Health Sciences University, Portland, Ore., USA
    Search for articles by this author
  • Daryl Kurozawa
    Affiliations
    From the Department of Surgery, Section of Surgical Endocrinology, Louisiana State University, New Orleans, La., USA

    Department of Surgery, Oregon Health Sciences University, Portland, Ore., USA
    Search for articles by this author
  • Eugene A. Woltering
    Correspondence
    Reprint requests: Eugene A. Woltering, MD, The James D. Rives Professor of Surgery, Chief, Section of Surgical Endocrinology, Louisiana State University, 1542 Tulane Ave., New Orleans, LA 701122822.
    Affiliations
    From the Department of Surgery, Section of Surgical Endocrinology, Louisiana State University, New Orleans, La., USA

    Department of Surgery, Oregon Health Sciences University, Portland, Ore., USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bloom S.R.
        • Mortimer C.M.
        • Thorner M.O.
        • et al.
        Inhibition of gastrin and gastric acid secretion by growth-hormone release inhibiting hormone.
        Lancet. 1974; 2: 1106-1109
        • Gerich J.E.
        • Lovinger R.
        • Grodsky G.M.
        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
        • Zandomeneghi R.
        • Montanari P.
        • Serra L.
        • et al.
        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
        • Liebow C.
        • Reilly C.
        • Serrano M.
        • Schally A.V.
        Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase.
        in: Proc Natl Acad Sci. 86. 1989: 2003-2007
        • Kokudo N.
        • Kothary P.
        • Eckhauser F.E.
        • Raper S.E.
        Inhibitory effects of somatostatin on rat hepatocyte proliferation are mediated by cyclic AMP.
        J Surg Res. 1991; 51: 113-118
        • Setyono-Han B.
        • Henkelman M.S.
        • Foekens J.A.
        • Klijn J.G.M.
        Direct inhibitory effects of somatostatin (analogues) on the growth of human breast cancer cells.
        Cancer Res. 1987; 47: 1566-1570
        • Rosenthal W.
        • Hescheler J.
        • Hinsch K.
        • Spicher K.
        • Trautwein W.
        • Schultz G.
        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
        • Heisler S.
        • Reisine T.D.
        • Hook V.Y.H.
        • Axelrod J.
        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
        • French M.B.
        • Moor B.C.
        • Lussier B.T.
        • Kraicer J.
        Protein kinase-C is not essential for growth hormone (GH)-releasing factor-induced GH release from rat somatotrophs.
        Endocrinology. 1989; 124: 2235-2344
        • Reisine T.
        Multiple mechanisms of somatostatin inhibition of adrenocorticotropin release from mouse anterior pituitary cells.
        Endocrinology. 1985; 116: 2259-2266
        • Woltering E.A.
        • Barrie R.
        • O'Dorisio T.M.
        • et al.
        Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane.
        J Surg Res. 1991; 50: 245-251
        • Dunn B.E.
        • Fitzharris T.P.
        • Barnett B.D.
        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
        • Folkman J.
        Angiogenesis: initiation and control.
        Ann N Y Acad Sci. 1982; 401: 212-226
        • Crum R.
        • Szabo S.
        • Folkman J.
        A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment.
        Science. 1985; 230: 1375-1378
        • Barrie R.
        • Woltering E.A.
        • Hajarizadeh H.
        • Mueller C.
        • Ure T.
        • Fletcher W.S.
        Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent.
        J Surg Res. 1993; 55: 446-450
        • Raynor K.
        • Murphy W.A.
        • Coy D.H.
        • et al.
        Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides.
        Mol Pharmacol. 1993; 43: 838-844
        • Raynor K.
        • O'Carroll A.
        • Kong H.
        • et al.
        Characterization of cloned somatostatin receptors SSTR4 and SSTR4.
        Mol Pharmacol. 1993; 44: 385-392
        • Zink A.
        • Scherubl H.
        • Kliemann D.
        • Hofiich M.
        • Ziegler R.
        • Raue F.
        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
        • Hsu W.H.
        • Xiang H.
        • Rajan A.S.
        • Kunze D.L.
        • Boyd A.E.
        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
        • Luini A.
        • De Matteis M.A.
        Evidence that receptor-linked G-protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells.
        J Neurochem. 1990; 54: 30-33
        • Vallar L.
        • Biden T.J.
        • Wollheim C.B.
        Guanine nucleotides induce Ca2+-independent insulin secretion from permeabilized RINm5F cells.
        J Biol Chem. 1987; 262: 5049-5065
        • Nilsson T.
        • Arkhammar P.
        • Rorsman P.
        • Berggren P.
        Suppression of insulin release by galanin and somatostatin is mediated by a G-protein.
        J Biol Chem. 1989; 264: 973-980
        • Schlegal W.
        • Winiger B.P.
        • Mollard P.
        • et al.
        Oscillations of cytosolic Ca2+ in pituitary cells due to action potentials.
        Nature. 1987; 329: 719-721
        • Chen C.
        • Israel J.
        • Vincent J.
        Electrophysiological responses of rat pituitary cells in somatotroph-enriched primary culture to human growth-hormone releasing factor.
        Neuroendocrinology. 1989; 50: 679-687
        • Pan M.G.
        • Florio T.
        • Stork P.J.S.
        G-protein activation of a hormone-stimulated phosphatase in human tumor cells.
        Science. 1992; 256: 1215-1217