adenylyl cyclase ac inhibitor sq22536  (Tocris)

Journal: Cellular and Molecular Life Sciences: CMLS

Article Title: GPR35 prevents drug-induced liver injury via the Gαs-cAMP-PKA axis in macrophages

doi: 10.1007/s00018-025-05751-4

Figure Lengend Snippet: GPR35 attenuates inflammatory response in macrophages through the Gαs-cAMP-PKA pathway. ( A ) Co-IP detection of GPR35 and Gαs in peritoneal macrophages stimulated with or without KA. ( B ) Levels of cAMP in peritoneal macrophages pretreated with FSK, KA, or DSCG. GPR35 agonist KA (4 mM), or DSCG (200 µg/ml) was administered 1 h before treatment with LPS. Adenylate cyclase activator FSK (10 µM) was used to stimulate cAMP in peritoneal macrophages 1 h before treatment with LPS. ( C ) Levels of TNF-α and IL-1β in supernatants from peritoneal macrophages after stimulation with LPS in the presence of FSK, KA, or DSCG. ( D ) Levels of TNF-α and IL-1β in supernatants from peritoneal macrophages with indicated pretreatment after LPS stimulation. ( E ) Levels of TNF-α and IL-1β in supernatants from peritoneal macrophages with indicated pretreatment after LPS stimulation. Gαs inhibitor NF449, AC inhibitor SQ22536, or PKA inhibitor H89 was added to the culture 30 min before treatment with GPR35 agonist KA or DSCG. The data are representative of three independent experiments and shown as the mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001

Article Snippet: To investigate the role of Gαs-cyclic AMP-protein kinase A (Gαs-cAMP-PKA) in the GPR35-mediated effect on macrophages, the Gαs inhibitor NF449 (25 µM, Santa Cruz Biotechnology, TEX, USA), AC inhibitor SQ22536 (50 µM, MedChemExpress, NJ, USA), or PKA inhibitor H89 (10 µM, MedChemExpress, NJ, USA), PKA inhibitor fragment [ – ] amide (10 μm, TargetMol, BOS, USA) was added to the culture 30 min prior to treatment with the GPR35 agonist.

Techniques: Co-Immunoprecipitation Assay

Journal: The Journal of Physiology

Article Title: Oxygen chemoreceptor inhibition by dopamine D₂ receptors in isolated zebrafish gills

doi: 10.1113/jp287824

Figure Lengend Snippet: Figure 6. Dopamine acts through intracellular secondary messenger cAMP in neuroepithelial cells (NECs) A, addition of SQ22536, an adenylyl cyclase (AC) inhibitor, decreased the effect of hypoxia on intracellular Ca2+. B, summary data treated as in (A) showing the mean ± SD F/F0 during the first 2 min of hypoxia exposure (Hypoxia-1), the reduction in the mean ± SD F/F0 during the entire duration of SQ22536 exposure (Hypoxia-2 + SQ22536; Kruskal–Wallis test, P = 0.010, n = 6 cells) and the mean ± SD F/F0 during the last 2 min of hypoxia exposure (Hypoxia-3). C, forskolin, an AC activator, partially recovered the suppressive effect of dopamine on the Ca2+

Article Snippet: To identify an intracellular mechanism for D2R, the AC inhibitor SQ22536 (catalog. no. 1435; Tocris) and AC activator forskolin (catalog. no. 11018; Cayman Chemical, Ann Arbor, MI) were tested.

Techniques:

Journal: Journal of Cancer

Article Title: Blockade of spinal dopamine D1/D2 receptor heteromers by levo -Corydalmine suppressed calcium signaling cascade in spinal neurons to alleviate bone cancer pain in rats

doi: 10.7150/jca.91129

Figure Lengend Snippet: D1DR and D2DR antagonists induced antinociception might be mediated by D1/D2DR heteromers. (A, B, C) The mechanical thresholds of TCI rats after coadministration of D1DR agonist SKF 38393 (2 μg/20 μL, i.t.), D2DR agonist Quinpride (2 μg/20 μL, i.t.), D1/D2DR heteromer agonist SKF 83959 (2 μg/20 μL, i.t.) respectively with D1DR antagonist SCH 23390 (20 μg/20 μL, i.t.). (D, E, F) The mechanical thresholds of TCI rats after co-administration of SKF 38393 (2 μg/20 μL, i.t.), Quinpride (2 μg/20 μL, i.t.), and SKF 83959 (2 μg/20 μL, i.t.) respectively with D2DR antagonist L-741,626 (20 μg/20 μL, i.t.) (SKF 38393, Quinpride and SKF 83959 were administrated 15 min before SCH 23390 or L-741,626 administration). (G) Time course of the mechanical thresholds of SD rats after a single administration of AC inhibitor SQ22536 (20 μg/20 μL), Gq inhibitor YM 254890 (2.5 μg/20 μL), PLC inhibitor U73122 (20 μg/20 μL), and IP3 inhibitor 2-APB (20 μg/20 μL) in TCI rats on the 14th day after the surgery. (H, I) The mechanical thresholds of TCI rats after coadministration of D1DR agonist SKF 83822 (2 μg/20 μL, i.t.) with SCH 23390 or L-741,626 (20 μg/20 μL, i.t.) (SKF 83822 was administrated 15 min before SCH 23390 and L-741,626 treatment) (n = 6, * P < 0.05, ** P < 0.01, compared with 0 h, # P < 0.05, ## P < 0.01, compared with control group, & P < 0.05, && P < 0.01, compared with TCI + D1DR/D2DR antagonist group).

Article Snippet: Furthermore, Gq inhibitor YM 254890, PLC inhibitor U73122, IP3 inhibitor 2-APB, and AC inhibitor SQ22536 could attenuate TCI-induced chronic bone cancer pain (Figure G).

Techniques: Control