Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1.
Morphine produces analgesia by activating mu opioid receptors encoded by the MOR-1 gene. Although morphine-6 beta-glucuronide (M6G), heroin and 6-acetylmorphine also are considered mu opioids, recent evidence suggests that they act through a distinct receptor mechanism. We examined this question in knockout mice containing disruptions of either the first or second coding exon of MOR-1. Mice homozygous for either MOR-1 mutation were insensitive to morphine. Heroin, 6-acetylmorphine and M6G still elicited analgesia in the exon-1 MOR-1 mutant, which also showed specific M6G binding, whereas M6G and 6-acetylmorphine were inactive in the exon-2 MOR-1 mutant. These results provide genetic evidence for a unique receptor site for M6G and heroin analgesia.
Schuller
A G
AG
Dept. of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscätaway 08854, USA.
King
M A
MA
Zhang
J
J
Bolan
E
E
Pan
Y X
YX
Morgan
D J
DJ
Chang
A
A
Czick
M E
ME
Unterwald
E M
EM
Pasternak
G W
GW
Pintar
J E
JE
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D005091:Exons / Q000235:genetics*; D003932:Heroin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology; D009022:Morphine Derivatives / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu; C035349:morphine-6-glucuronide; D003932:Heroin; C026979:6-O-monoacetylmorphine