Dermorphin is a natural opioid that binds as an agonist with high potency and selectivity to mu opioid receptors found in amphibian skin.Dermorphin is about 30–40 times more potent than morphine.
Dermorphin, a peptide isolated from the skin of Phyllomedusa frogs and the peptide receptor (NOP) component by the endogenous agonist nociceptin/orphanin FQ (N/OFQ). In displacement binding studies at CHOhMu, Dermorphin and DeNo displac the binding of [3H]-DPN in a concentration dependent and saturable manner. Dermorphin displays an affinity of 7.17, while N/OFQ fails to displace [3H]-DPN at the Delta receptor. Dermorphin and DeNo stimulate the binding of GTPγ[35S] in a concentration dependent and saturable manner at the Mu receptor.
Dermorphin is not found in humans or other mammals and similar D-amino acid peptides have only been found in bacteria, amphibians, and molluscs.
Dermorphin appears to be made in these through an unusual posttranslational modification carried out by an amino acid isomerase. This unusual process is needed because the D-alanine in this peptide is not among the 20 amino acids coded for in the genetic code and thus the peptide cannot be synthesized in the usual way from the encodings in the genome of an organism.
Dermorphin and Hyp6-dermorphin are the first representatives of a new class of potent opioid peptides occurring in amphibian skin. They present the unique feature of having a D-Ala residue incorporated in the peptide molecule.
Dermorphin displayed a potent depressive action on electrically stimulated contractions of the guinea-pig ileum and mouse vas deferens preparations. Dermorphin was respectively 57,294, 18 and 39 times more potent than Met-enkephalin, Leu-enkephalin, beta-endorphin, and morphine on the guinea-pig ileum opiate receptors. On the vas deferens receptors, dermorphin was about as potent as the enkephalins and 40 times more potent than morphine. Naloxone was a powerful antagonist to dermorphin in both preparations. Morphine was 752 and 2170 times less potent, depending on the analgesia test used. At high intracerebroventricular doses analgesia was accompanied by catalepsy.
Intracerebroventricular infusion of dermorphin induced development of tolerance and precipitation of withdrawal symptoms upon administration of naloxone. Both tolerance and physical dependence was consistently less marked with dermorphin than with morphine.
The minimum sequence requirement for full dermorphin activity was represented by the N-terminal tetrapeptide. The presence of the D-Ala2-residue was of crucial importance.
Post time: Jan-06-2026