Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis.
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 vanadate (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.
Patel
P C
PC
Department of Surgery, Louisiana State University, New Orleans.
Barrie
R
R
Hill
N
N
Landeck
S
S
Kurozawa
D
D
Woltering
E A
EA
D000818:Animals; D002642:Chick Embryo; D000242:Cyclic AMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D015282:Octreotide / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D015398:Signal Transduction
D000242:Cyclic AMP; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins; D015282:Octreotide