Antiproliferative and GH-inhibitory activity of chimeric peptides consisting of GHRP-6 and somatostatin.
Chimeric peptides consisting of growth hormone releasing peptide (GHRP-6) linked to somatostatin (6-11) via an amide bond to provide the effector parts of both the peptides were synthesized. The anti-proliferative, cytotoxic, and GH-inhibitory activities of these chimeric peptides were determined in vitro in the rat pituitary adenoma cell line GH3. One of the chimeric peptides, GSD, exhibited significantly greater (p < 0.001) anti-neoplastic and GH-inhibitory activity, as compared to RC-160. The hybrid peptides displayed high affinity binding to somatostatin receptors on GH3 cells. The bioactivity of GSD was found to be mediated by the stimulation of tyrosine phosphatase, involving a cGMP-dependent pathway, through pertussis toxin-sensitive G-proteins. Such potent GH-inhibitory chimeric peptides may be of potential importance in the therapy of acromegaly, as well as provide novel tools to study the regulation of GH secretion by GHRP and somatostatin.
Dasgupta
P
P
NeuroImmunology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg (J.N.U. Campus), New Delhi, 110067, India.
Singh
A T
AT
Mukherjee
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D013006:Growth Hormone / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; C051458:vapreotide; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D013006:Growth Hormone; D017027:Protein Tyrosine Phosphatases; D006152:Cyclic GMP