DERMORPHIN-RELATED PEPTIDES FROM THE SKIN OF PHYLLOMEDUSA-BICOLOR AND THEIR AMIDATED ANALOGS ACTIVATE 2 MU-OPIOID RECEPTOR SUBTYPES THAT MODULATE ANTINOCICEPTION AND CATALEPSY IN THE RAT

被引:50
作者
NEGRI, L [1 ]
ERSPAMER, V [1 ]
SEVERINI, C [1 ]
POTENZA, RL [1 ]
MELCHIORRI, P [1 ]
ERSPAMER, V [1 ]
机构
[1] CNR,INST NEUROBIOL,I-00185 ROME,ITALY
关键词
LYS(7)DERMORPHIN; TRP(4); ASN(7)]DERMORPHIN; ASN(5)]DERMORPHIN-(1-5); GUINEA PIG ILEUM; MOUSE VAS DEFERENS;
D O I
10.1073/pnas.89.15.7203
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7203 / 7207
页数:5
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