Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two mu opioid receptor subtypes that modulate antinociception and catalepsy in the rat.

Abstract

Three naturally occurring dermorphin-like peptides from the skin of the frog Phyllomedusa bicolor, the related carboxyl-terminal amides, and some substituted analogs were synthesized, their binding profiles to opioid receptors were determined, and their biological activities were studied in isolated organ preparations and intact animals. The opioid binding profile revealed a very high selectivity of these peptides for mu sites and suggested the existence of two receptor subtypes, of high and low affinity. The peptides tested acted as potent mu opioid agonists on isolated organ preparations. They were several times more active in inhibiting electrically evoked contractions in guinea pig ileum than in mouse vas deferens. When injected into the lateral brain ventricle or peritoneum of rats, the high-affinity-site-preferring ligand, [Lys7-NH2]dermorphin, behaved as a potent analgesic agent. By contrast, the low-affinity-site-preferring ligand, [Trp4,Asn7-NH2]dermorphin, produced a weak antinociception but an intense catalepsy.

• Authors: L Negri, G F Erspamer, C Severini, R L Potenza, P Melchiorri, V Erspamer
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 89 Issue 15 Pg. 7203-7 (Aug 01 1992) ISSN: 0027-8424 [Print] United States
• PMID: 1353890 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Enkephalins
• Oligopeptides
• Opioid Peptides
• Receptors, Opioid
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Receptors, Opioid, mu
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• dermorphin
• Naloxone

Topics

• Amino Acid Sequence
• Analgesics, Opioid (pharmacology)
• Animals
• Anura
• Binding, Competitive
• Brain (metabolism)
• Catalepsy (physiopathology)
• Cerebral Ventricles (drug effects, physiology)
• Electric Stimulation
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• Enkephalins (metabolism)
• Guinea Pigs
• Injections, Intraventricular
• Kinetics
• Molecular Sequence Data
• Myenteric Plexus (drug effects, physiology)
• Naloxone (pharmacology)
• Nociceptors (physiology)
• Oligopeptides (administration & dosage, isolation & purification, pharmacology)
• Opioid Peptides
• Pain (physiopathology)
• Rats
• Receptors, Opioid (drug effects, metabolism, physiology)
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Receptors, Opioid, mu
• Skin (chemistry)
• Skin Physiological Phenomena
• Structure-Activity Relationship