The effects of peptide histidine isoleucine on antral gastrin and somatostatin.
The present studies were directed to determine whether peptide histidine isoleucine (PHI) affects expression of the gastrin and somatostatin genes and whether such effects may be functionally linked. In separate experiments, the effects of PHI on medium gastrin and somatostatin concentrations, the incorporation of 35S-labelled amino acids into newly synthesized gastrin and somatostatin, and steady state gastrin and somatostatin mRNA were determined. PHI inhibited basal expression of the gastrin gene at all levels examined, while no significant effect on basal somatostatin gene expression could be detected. PHI also decreased carbachol-stimulated antral gastrin release and simultaneously increased somatostatin release. However, in contrast to its structural analogues, secretin and gastric inhibitory peptide, the immunoneutralization of endogenous somatostatin by the administration of specific antibodies did not affect significantly the capacity of PHI to inhibit gastrin release into the culture medium stimulated by carbachol. The results of these studies indicate that PHI exerts a physiological inhibitory effect on antral gastrin cells and that this inhibition may occur at several steps along the biosynthetic pathway. In addition, unlike its structural analogues, PHI inhibition of carbachol-stimulated gastrin release is not functionally linked to its stimulatory effects on somatostatin release.
Harvard Digestive Diseases Center, Brigham and Women's Hospital, Boston, MA 02115.
M M
MM
Wolfe
R
R
Chang
M E
ME
Mailliard
P S
PS
Karnik
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000378:metabolism; D010451:Peptide PHI / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000096:biosynthesis*
D005755:Gastrins; D010451:Peptide PHI; D012333:RNA, Messenger; D013004:Somatostatin; D002217:Carbachol; D008715:Methionine; D003545:Cysteine