European journal of pharmacology
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Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels have been suggested to play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study showed that the selective HCN channels blocker, ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride) can block the induction of long-term potentiation (LTP) in perforant path-CA3 region in rat hippocampus in vivo. ⋯ In addition, ZD7288, when given 30 min after HFS, did not alter the maintenance of LTP. The results suggest that ZD7288 has the ability to prevent the induction of LTP at the Schaffer collateral-CA1 synapse of rat hippocampus, and that this inhibitory effect is attenuated by direct activation of the NMDA receptor.
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The possible antiallodynic effect of phosphodiesterase 5 inhibitor sildenafil and nitric oxide donor glyceryl trinitrate as well as the changes in phosphodiesterase 5A2 mRNA expression in dorsal root ganglion and spinal cord of allodynic diabetic rats was assessed. Diabetes was induced by streptozotocin (50mg/kg, i.p.) in male Wistar rats. Streptozotocin injection produced hyperlglycemia, polydipsia, polyphagia and polyuria as well as long-term tactile allodynia (12 weeks) and a reduction of phosphodiesterase 5A2 mRNA expression in spinal cord of diabetic rats. ⋯ Moreover, both drugs reversed streptozotocin-induced phosphodiesterase 5A2 mRNA expression reduction. Our results indicate that glyceryl trinitrate and sildenafil reduce tactile allodynia in diabetic rats suggesting that nitric oxide and cyclic GMP supply is an important step in their mechanism of action of these drugs in diabetic animals. Data suggest that nitric oxide donors (as glyceryl trinitrate) and drugs which increase cyclic GMP levels (as sildenafil) could have a role in the pharmacotherapy of tactile allodynia in diabetic patients.