Effect of bucladesine, pentoxifylline, and H‐89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain

Abstract

The aim of this study was to determine the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal nociception in a mouse model of acute pain. Here, we studied the effect of H-89 (protein kinase A inhibitor), bucladesine (Db-cAMP) (membrane-permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H-89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db-cAMP (50, 100, and 300 nm/mouse) were administered intraperitoneally (I.p.) 15 min before a tail-flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail-flick test, respectively. I.p. administration of H-89 and PTX significantly decreased the thermal-induced pain sensation in their low applied doses. Db-cAMP, however, decreased the pain sensation in a dose-dependent manner. The highest applied dose of H-89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db-cAMP in doses of 50 and 100 nm/mouse. Surprisingly, Db-cAMP decreased the antinociceptive effect of the lowest dose of H-89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H-89 on pain sensation; however, the highest dose of H-89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co-administration of Db-cAMP and PTX increased the antinociceptive effect of each compound on thermal-induced pain. In conclusion, PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases.

Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA‑CREB‑BDNF signaling pathway

“…The results demonstrated that hippocampal BDNF levels were significantly decreased in rats treated with Sev, with the loss of granule neurons and inhibition of the PKA/CREB/BDNF signaling pathway. Cognitive impairment caused by Sev was partially reversed by the activation of the PKA/CREB/BDNF signaling pathway following the administration of the PKA agonist Buc (21). These results indicated that cognitive deficiencies caused by Sev may be restored by activation of the PKA/CREB/BDNF pathway.…”

Melatonin alleviates traumatic brain injury‑induced anxiety‑like behaviors in rats: Roles of the protein kinase A/cAMP‑response element binding signaling pathway

“…no. HY-B0764A; MedChemExpress) selectively activates cAMP-dependent protein kinase (PKA) ( 27 ). H89 and dbcAMP were dissolved in saline (containing 10% dimethyl sulfoxide and 20% sulfobutylether β-cyclodextrin) and were applied by stereotactic injection 15 min before surgery.…”

Opioidergic System-Mediated Antinociceptive Activity of Tofisopam

“…Bu moleküllerin özellikle fosfodiesterazların (PDE) çeşitli izoenzimlerine yüksek afinite ile bağlandıkları ve onları inhibe ettikleri rapor edilmiştir [8,13]. Literatürde PDE inhibitörlerinin akut ve kronik ağrıda etkili bulunduğuna dair çok sayıda çalışma mevcuttur [14][15][16][17][18][19]. Örneğin rolipram, teofilin ve sildenafil'in deney hayvanlarında asetik asitle indüklenmiş kıvranma testi yanıtlarını iyileştirdikleri [20][21][22]; zaprinast, ibudilast ve rolipram'ın ise nöropatik ağrıda faydalı etkiler gösterdikleri rapor edilmiştir [17,23].…”