Determination of the structural requirements for the inhibitory action of gastrin-releasing peptide on growth hormone release.
We have previously determined that gastrin-releasing peptide (GRP) suppresses plasma growth hormone (GH) levels and blocks the response to growth hormone releasing factor (GRF) following its injection into the third ventricle (3V) of conscious male rats. To determine the portion of the peptide required for this action, fragments of the peptide were injected at various doses to determine their effect on plasma growth hormone and the response to a test dose of GRF (1 microgram/kg IV). The GRP 1-16 lowered plasma GH and blocked the response to GRF following an intraventricular injection of 2 micrograms but not 0.2 microgram of the peptide. Carboxy-terminal fragments were more effective. AcGRP20-27 was partially effective at a 100 times lower dose of 2.0 ng, a result similar to that obtained with the related peptide, bombesin. Even the C-terminal heptapeptide AcGRP-27 was effective at a dose of 2 ng. The results indicate that the C-terminal heptapeptide is the minimal requirement for intraventricularly injected GRP to suppress plasma GH levels and block the response to GRF.
Kentroti
S
S
University of Colorado, Health Sciences Center, Denver 80262.
McCann
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D019886:Gastrin-Releasing Peptide; D013006:Growth Hormone / Q000378:metabolism*; D007276:Injections, Intraventricular; D008969:Molecular Sequence Data; D010052:Ovariectomy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D010446:Peptide Fragments; D010455:Peptides; D019886:Gastrin-Releasing Peptide; D013006:Growth Hormone; D001839:Bombesin