bms 193885  (Merck & Co)

Journal: Molecular Brain

Article Title: Identification of VGLUT3-expressing LTMRs-recruited spinal circuits for itch inhibition

doi: 10.1186/s13041-025-01245-3

Figure Lengend Snippet: VGLUT3 + sensory fibers alleviate mechanical and chemical itch via spinal NPY-Y1R and DYN-KOR-signaling pathway, respectively. A, F Schematic of experimental design. B, C Pretreatment of Y1 receptor antagonist (BMS193885) does not alter the inhibitory effect of VGLUT3 + fibers on both histamine and chloroquine itch models. D, E Pretreatment of BMS193885 abrogates the inhibitory effect of VGLUT3 + fibers on mechanical itch and reduces the degree of inhibition. G, H Pretreatment of KOR antagonist (norBNI) attenuates the degree of itch inhibition mediated by VGLUT3 + fibers on both histamine and chloroquine itch models. I,J Pretreatment of KOR antagonist (norBNI) does not alter VGLUT3 + fiber-mediated suppression of mechanical itch. Data are represented as mean with SEM and assessed using two-tailed unpaired t test, exact p-values are reported for all statistical comparisons

Article Snippet: The nor-Binaltorphimine (nor-BNI) (Cat# AB120078 , Abcam) and BMS193885 (Cat#HY-120619, MCE) were dissolved in saline.

Techniques: Inhibition, Two Tailed Test

Journal: Molecular Brain

Article Title: Identification of VGLUT3-expressing LTMRs-recruited spinal circuits for itch inhibition

doi: 10.1186/s13041-025-01245-3

Figure Lengend Snippet: Schematic model of the spinal inhibitory circuit for DRG VGLUT3 -mediated suppression of itch. A Optogenetic activation of VGLUT3-expressing LTMR terminals inhibits itch signaling in the spinal cord through distinct pathways. Chemical itch is suppressed via a dynorphin (DYN)-mediated inhibitory pathway, where VGLUT3⁺ LTMR activation recruits DYN⁺ inhibitory interneurons to suppress κ-opioid receptor (KOR)-expressing pruriceptive neurons. This anti-pruritic effect is abolished by the selective KOR antagonist norBNI. B Mechanical itch is inhibited through a distinct neuropeptide Y (NPY)-dependent pathway, where VGLUT3⁺ LTMR activation recruits NPY⁺ inhibitory interneurons to suppress itch-transmission neurons via Y1 receptor (Y1R) signaling. This anti-pruritic effect is selectively blocked by the Y1R antagonist BMS193885

Article Snippet: The nor-Binaltorphimine (nor-BNI) (Cat# AB120078 , Abcam) and BMS193885 (Cat#HY-120619, MCE) were dissolved in saline.

Techniques: Activation Assay, Expressing, Transmission Assay

Journal: eLife

Article Title: Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

doi: 10.7554/eLife.86633

Figure Lengend Snippet: ( A ) The experimental approach taken to generate the data presented in ( B, C ). ( B, C ) Vehicle control-treated AAV.flex.hM3Dq-mCherry spinal-injected Npy-Cre mice display marked reductions in mechanical withdrawal threshold (MWT) ( B ) and withdrawal latency to radiant heat ( C ) of the ipsilateral paw 2 days after intraplantar injection of complete Freund’s adjuvant (CFA). Both mechanical and thermal hypersensitivity are blocked in clozapine- N -oxide (CNO)-treated mice ( n = 10 vehicle group, 8 CNO group). ( D ) The experimental approach taken for the data presented in ( E, F ). Drug treatments were administered using a crossover design ( n = 9). ( E, F ) Marked reductions in MWT ( E ) and withdrawal latency to radiant heat ( F ) are observed following spared nerve injury (SNI). These are blocked by CNO treatment, and this blockade persists in the presence of the Y1 antagonist BMS 193885 (BMS). ( G ) The experimental approach taken for the data presented in ( H–J ). Acc. = acclimation; Pre. = pre-conditioning; Con. = conditioning. ( H ) Neither wild-type control nor AAV.flex.hM3Dq-mCherry spinal-injected Npy-Cre mice displayed a conditioned place preference (CPP) to CNO following SNI ( n = 7). ( I ) Heat maps of a representative mouse from each group demonstrating position and time spent in each chamber during preconditioning and post-conditioning test days. ( J ) A marked increase in the time spent responding to application of acetone to the ipsilateral paw (shaking, lifting, and/or licking) is seen in vehicle-treated AAV.flex.hM3Dq-mCherry spinal-injected Npy-Cre mice following SNI. This cold hypersensitivity is blocked when the same mice are treated with CNO ( n = 8). Data are shown as individual values with mean ± standard error of the mean (SEM). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; repeated-measures two-way ANOVA with Šidák’s post-test in ( B, C, H ), repeated-measures one-way ANOVA with Šidák’s post-test in ( E , F, J ).

Article Snippet: For some experiments, the Y1 antagonist BMS 193885 (Bio-Techne, Abingdon, UK) dissolved in a 40% PEG-400/60% sterile saline mixture was co-injected i.p. at a dose of 10 mg/kg with CNO; co-injection of the respective vehicles for CNO and BMS 193885 was used as a control.

Techniques: Injection, Adjuvant, Conditioned Place Preference