title: Structure-activity relationship of dermorphin on gastric secretion.
abstract: The amphibian skin heptapeptide dermorphin (DM) administered intracerebroventricularly to rats significantly reduces gastric secretion. Dermorphin and 19 DM homologs and analogs were tested for their effect on gastric volume, pH, H+ ion concentration, and gastric acid output. DM, DM N-terminal pentapeptide and tetrapeptide amides, [D-Met2]DM, [Sar4]DM, [Trp5]DM, [Phe5]DM, [Gly7]DM, [Ser(Bzl)7]DM, and deamidated-DM significantly (P less than 0.01) reduced gastric acid output 2 h after injection. These data provide evidence for the following conclusions on the effect of DM on gastric secretion: ability to inhibit gastric secretion depends on the presence of the D-isomer of Ala at position 2, since [L-Ala2]DM is inactive; the shortest sequence with significant bioactivity is DM N-terminal tetrapeptide amide; the single replacement of amino acid residues in DM elicits a wide range of activities, varying from full biological activity of [Gly7]DM to those analogs with a complete lack of activity, such as [Pro4]DM and [Gly6]DM; and 4) coupling of protective groups to amino and hydroxyl groups of DM results in a significant loss of activity.
mesh_terms: D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018847:Opioid Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin