Recently, antisera that recognize unique epitopes of the cloned p-, S-, and K-opioid receptors (MOR, DOR, KOR, respectively) have been developed. In the present study MOR-, DOR-, and KOR-like immunoreactivities (Lls) were examined in rat dorsal root ganglia (DRGs, L4-5) after injection of carrageenan (CAR) into the hindpaw. In normal control rats, 20.9%, 13.5%, and 9% of the DRG neurons contain...

The hypothesis that functionally selective G protein-coupled receptor (GPCR) agonists may have enhanced therapeutic benefits has revitalized interest for many GPCR targets. In particular, although κ-opioid receptor (KOR) agonists are analgesic with a low risk of dependence and abuse, their use is limited by a propensity to induce sedation, motor incoordination, hallucinations, and dysphoria-lik...

The κ-opioid receptor (KOR) and bradykinin B2 receptor (B2R) are involved in a variety of important physiological processes and share many similar characteristics in terms of their distribution and functions in the nervous system. We first demonstrated the endogenous expression of KOR and B2R in human SH-SY5Y cells and their co-localization on the membrane of human embryonic kidney 293 (HEK293)...

Nitric oxide (NO) suppressed the transcription of the mouse kappa opioid receptor (KOR) gene, mediated by a rapid downregulation of c-myc gene expression. KOR was constitutively expressed in postnatal day 19 (P19) embryonal carcinoma stem cells and is suppressed by NO donors [sodium nitroprusside (SNP), 3-morpholinosydnonimine-1, and S-nitrosoglutathione] in P19 stem cells within 4 hr. The supp...

The opioid system (opioid peptides and receptors) regulates a variety of neurophysiologic functions, including pain control. Here we show novel roles of the κ opioid system in vascular development. Previously, we revealed that cAMP/protein kinase A (PKA) signaling enhanced differentiation of vascular progenitors expressing VEGF receptor-2 (fetal liver kinase 1; Flk1) into endothelial cells (ECs...

The dynorphin (Dyn) A analogue zyklophin ([N-benzyl-Tyr(1)-cyclo(d-Asp(5),Dap(8))]dynorphin A(1-11)NH2) is a kappa opioid receptor (KOR)-selective antagonist in vitro, is active in vivo, and antagonizes KOR in the CNS after systemic administration. Hence, we synthesized zyklophin analogues to explore the structure-activity relationships of this peptide. The synthesis of selected analogues requi...

Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid s...

The molecular mechanisms mediating stress-induced dysphoria in humans and conditioned place aversion in rodents are unknown. Here, we show that repeated swim stress caused activation of both -opioid receptor (KOR) and p38 mitogen-activated protein kinase (MAPK) coexpressed in GABAergic neurons in the nucleus accumbens, cortex, and hippocampus. Sites of activation were visualized using phosphose...

BACKGROUND Butorphanol is an opioid analgesic with partial agonist actions at micro- and kappa-opioid receptors (MOR and KOR). Previous studies have demonstrated that both MOR antagonists and KOR agonists are effective in alleviating intrathecal morphine-induced itch in primates. The aim of the study was to investigate the effectiveness of butorphanol as an antipruritic and to elucidate the rec...