Structure‐activity relationships of eighteen somatostatin analogues on gastric secretion.

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Abstract
The effect of somatostatin and 18 somatostatin analog on pentagastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogs are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. The ID50 [median inhibitory dose] for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 .mu.g kg-1 h -1 was found to be 1.29 .+-. 0.13 nmol kg-1 h-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. D-Phe6, D-Phe7, D-Thr10, DThr12 and D-Phe6-D-Trp8 analog all show low biological activity against the secretion of gastric acid and pepsin, growth hormone (GH), insulin and glucagon. None of these analogs are antagonists of the cyclic-somatostatin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. The analogs under investigation show parallel activity changes against gastric and GH secretion, suggesting a similarity between the gastric and GH receptors for somatostatin. D-Cys14 analog are equipotent with or have a greater potency than cyclic-somatostatin in inhibiting gastric acid secretion, GH and glucagon, but show low insulin inhibiting activity.