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Morphine-6 beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To define more fully the importance of this compound in morphine action, we have compared the analgesic actions of morphine and its 6 beta-glucuronide metabolite after both peripheral and central administration. Given s.c., morphine-6 beta-glucuronide elicited(More)
Understanding the pharmacology of opioid receptors took a major step forward with the cloning of genes that encode four members of the opioid receptor family. Gavril Pasternak and Kelly Standifer show how strategies that use antisense oligodeoxynucleotides can provide a selective approach to correlate the properties of the cloned receptors with their in(More)
Antisense oligodeoxynucleotides (18-20 bases) to a cloned delta opioid receptor (DOR-1) lower delta binding in NG108-15 cells by 40%-50%. Changing 4 bases to generate a mismatch antisense oligodeoxynucleotide or mixing the corresponding sense and antisense oligodeoxynucleotides prior to treatment of the cells eliminates the inhibition of binding, confirming(More)
Central morphine analgesia is significantly greater in male than in female rats. Since mu and delta opioid receptor subtypes have been implicated in supraspinal analgesia, the present study evaluated whether gender or adult gonadectomy altered (a) analgesia on the tail-flick and jump tests following central administration of the mu-selective agonist,(More)
Derivatives carrying a substituent in the para position of the phenyl group of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl] carbostyril (10) were prepared and their effects on beta-adrenoceptors evaluated in vitro. Unsubstituted compound 10, iodo 11, amino 12, and bromoacetamido 13 derivatives (all racemic) bound to the receptor with(More)
The present study evaluated the central effects of beta-funaltrexamine (B-FNA), a non-equilibrium antagonist of mu-opioid receptors and a reversible agonist of kappa-opioid receptors upon food intake in rats under freely-feeding, deprivation and glucoprivic conditions. B-FNA elicited distinct short-term and long-term actions, consistent with binding studies(More)
The interaction of the carbostyril derivatives 5-[2-[[1-(4-aminophenyl)-2-methyl-prop-2-yl]amino]-1-hydroxyethyl]-8-hydroxycarbostyril (carbo-amine) and 5-[2[[3-[4-(bromoacetamido)phenyl]-2-methylprop-2-yl]amino]1-hydroxyethyl]-8-hydroxycarbostryril (carbo-Br) with the rat reticulocyte beta-adrenoreceptor system has been partially characterized. In the(More)
Syntaxins 1 through 4 are SNAP receptor (SNARE) proteins that mediate vesicular trafficking to the plasma membrane. In retina, syntaxins 1 and 3 are expressed at conventional and ribbon synapses, respectively, suggesting that synaptic trafficking functions differ among syntaxin isoforms. To better understand syntaxins in synaptic signaling and trafficking,(More)
Behaviorally, sigma1 agents modulate opioid analgesia. To examine possible mechanisms responsible for these interactions, we have identified a cell line containing both sigma1 and opioid receptors. [3H](+)-pentazocine binding in BE(2)-C human neuroblastoma cells is high affinity (KD 3.4±0.7 nM) and high density (Bmax 2.98±0.14 pmol/mg protein). Competition(More)
The molecular mechanism(s) underlying cross-tolerance between mu and opioid receptor-like 1 (ORL1) receptor agonists were investigated using two human neuroblastoma cell lines endogenously expressing these receptors and G protein-coupled receptor kinases (GRKs). Prolonged (24 h) activation of the mu receptor desensitized both mu and ORL1 receptor-mediated(More)