A study in this issue of Molecular Pharmacology on agonist-induced internalization of mu-opioid receptors during long-term opiate drug exposure is discussed. The study demonstrates the critical role of re-cycling of reactivated mu receptors back to the plasma membrane for the maintenance of agonist signaling during long-term opiate exposure.

Systemic administration of resiniferatoxin (RTX), an ultrapotent capsaicin analogue, removes transient receptor potential vanilloid type 1 (TRPV1)-expressing afferent neurons and impairs thermal but not mechanical nociception in adult animals. In this study, we determined how loss of TRPV1-expressing sensory neurons alters the antinociceptive effect of mu opioids and mu opioid receptors in the ...

Endomorphin-1 is a short-chain neuropeptide with a high affinity fo the mu-opioid receptor and has recently been localized in acutely inflamed knee joints where it was found to reduce inflammation. The present study examined the propensity of endomorphin-1 to modulate synovial blood flow in normal and adjuvant-inflamed at knee joints. Under deep urethane anesthesia, endomorphin-1 was topically ...

The involvement of mu-opioid receptors in different behavioral responses elicited by nicotine was explored by using mu-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by n...

Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled and activate inhibit...

To elucidate the mechanism of the cellular antiopioid activity of neuropeptide FF (NPFF), we have transfected the SH-SY5Y neuroblastoma cell line, which expresses mu-and delta-opioid receptors, with the human NPFF2receptor. The selected clone, SH2-D9, expressed high-affinity NPFF2 receptors in the same range order as mu- and delta-opioid receptors (100-300 fmol/mg of protein). The NPFF analog [...

Heterodimerization of G-protein coupled receptors has become increasingly recognized as a valuable mechanism to increase receptor diversity. Heterodimers have been observed in the opioid receptor family, but one of the most intriguing is that formed between mu and delta opioid receptors. In this issue of Neuron He et al. present evidence further implicating these heterodimers in morphine tolera...

CONTEXT The endogenous opioid system and opioid mu receptors (mu-receptors) are known to interface environmental events, positive (eg, relevant emotional stimuli) and negative (eg, stressors), with pertinent behavioral responses and to regulate motivated behavior. OBJECTIVE To examine the degree to which trait impulsiveness (the tendency to act on cravings and urges rather than to delay grati...

Opioid receptor binding, including the mu, delta, and kappa receptor subtypes, was compared in morphine-injected and control rats. Brain tissues were homogenized and centrifuged either one or two times prior to receptor binding assay. In brain membranes from morphine-injected rats centrifuged once, there was a decrease in mu, but not delta or kappa, binding compared to controls, perhaps indicat...

Intestinal gluconeogenesis is involved in the control of food intake. We show that mu-opioid receptors (MORs) present in nerves in the portal vein walls respond to peptides to regulate a gut-brain neural circuit that controls intestinal gluconeogenesis and satiety. In vitro, peptides and protein digests behave as MOR antagonists in competition experiments. In vivo, they stimulate MOR-dependent ...