Structure-activity studies with somatostatin: the role of tryptophan in position 8.
The gastric acid and pepsin inhibitory activities of 21 analogues of somatostatin, the majority modified at position 8, were determined in conscious cats in order to examine the importance of Trp8 for the activity of somatostatin. Pepsin secretion stimulated by pentagastrin was 5 times more sensitive, compared with the acid secretion, to inhibition by somatostatin. All the analogues showed similar differential sensitivity, indicating a similar specificity of somatostatin receptors involved in the inhibition of these two secretions. Halogenated-Trp8 analogues of somatostatin were only equipotent or slightly more active than somatostatin against gastric secretion in the cat, whilst these analogues are up to 30 times more potent against growth hormone release in the rat, indicating a different specificity of the two groups of receptors. Studies with the position 8 modified analogues suggest that the electron density of the aromatic nucleus of Trp8 may be relatively unimportant in determining the gastric inhibitory activity, whilst it can be concluded that the role of Trp8 in somatostatin depends to a large extent on the indole NH group. The precise role of Trp8 in somatostatin could be an involvement in the binding of somatostatin to its receptors, or involvement in forming the biologically active conformation of somatostatin.
D000818:Animals; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D010418:Pentagastrin / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014364:Tryptophan
D013004:Somatostatin; D014364:Tryptophan; D010434:Pepsin A; D010418:Pentagastrin