Dimeric dermorphin peptides: central administration suppresses gastric acid secretion through interaction with mu-type opioid receptor.
The effect of centrally administered dermorphin and a series of dimeric dermorphin analogs on gastric acid secretion was studied in pylorusligated rats. Dimeric dermorphin analogs consist of identical peptide chains either directly linked with a dihydride bond or a polyethyleneamine bridge at their carboxy termini. At a dose of 0.5 nmol dermorphin, and the dimeric analogs di-[D-Arg2,Sar4]-tetra-DM2, di-penta-DM0, di-[Sar4]-penta-DM0, di-[D-Arg2,Sar4]-penta-DM0, di-[D-Ala4]-penta-DM0 and di-DM0, and di-DM0, inhibited gastric acid output in a statistically significant manner (P less than 0.05). Furthermore, the binding characteristics of these peptides for the mu-type opioid receptor were analyzed using a brain synaptosomal fraction. Dermorphin and several dimeric dermorphin peptides bound to the mu-receptor: di-penta-DM0, di-[Sar4]-penta-DM0, di-penta-DM2 and di-DM0, had 3-to 5-fold greater affinity for the mu-receptor than the specific mu-agonist DAGO. These data indicate that a correlation exists between the central mediated gastric inhibitory effect of DM and several dimeric analogs and their affinity for the mu-type opioid receptor in rat brain.
Guglietta
A
A
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental and Health Sciences, Research Triangle Park, NC 27709.
Irons
B J
BJ
Lazarus
L H
LH
de Castiglione
R
R
Melchiorri
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018847:Opioid Peptides; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu
D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C030058:dermorphin