Parkinson＇s disease （PD） is the most common motor neurode- generative disorder affecting approximately 4 million people worldwide. Although PD presents primarily with motor dysfunction, non-motor symptoms including...Parkinson＇s disease （PD） is the most common motor neurode- generative disorder affecting approximately 4 million people worldwide. Although PD presents primarily with motor dysfunction, non-motor symptoms including cognitive decline, mood disorders, reduced olfaction and constipation are also of- ten present, with some of these non-motor symptoms even pre- senting prior to the onset of motor symptoms. It is well known that PD is largely caused by the gradual degeneration of dopa- minergic neurons within the substantia nigra pars compacta （SNc）, along with the presence of protein aggregates called Lewy bodies, which consist primarily of ct-synuclein and are found in the cytoplasm of surviving neurons. This ongoing cell loss and Lewy body pathology is not confined to the SNc, but is also seen in other brain regions implicated in PD pathogenesis such as the locus ceruleus.展开更多
The expression of the types of tachykinin receptors in the dorsal root ganglion (DRG) neurons by means of Xenopus oocyte expressing system was studied. Poly(A) +RNAs were extracted from cat cervical and lumbar DRG. Tw...The expression of the types of tachykinin receptors in the dorsal root ganglion (DRG) neurons by means of Xenopus oocyte expressing system was studied. Poly(A) +RNAs were extracted from cat cervical and lumbar DRG. Two days after injection of Poly(A) +RNAs, the oocytes were recorded with the two electrode voltage clamp technique. In the oocytes injected with DRG poly(A) +RNA,[Sar 9,Met(O 2) 11 ] substance P(Sar SP, 1 μmol/L), neurokinin A (NKA,1 μmol/L) or [β Ala 8] neurokinin A (4-10) (Ala NKA, 1 μmol/L) produced an inward current comprising a rapid spike and a long sustained oscillatory component for several minutes. Sar SP induced response was blocked by NK 1 antagonist L 668, 169 (1 μmol/L), but not by NK 2 antagonist L 659,877(1μmol/L). In contrast, Ala NKA and NKA responses were only blocked by L 659,877. The oocytes injected with DH Poly(A) +RNA also responded to Sar SP and NKA with similar inward currents, which were selectively blocked by L 668,169 and L 659,877, respectively. These tachykinins induced responses had a potent desensitization. The present data indicate expression of NK 1 and NK 2 receptors in DRG neurons, suggesting that there may be tachykinin autoreceptors on the nociceptive primary afferent terminals.展开更多
Objective To evaluate effect of Neurokinin receptor antagonist on the prevention from hyper-pnea-induced bronchoconstriction using a dual Neurokinin receptor antagonist FK224. Methods 12 pathogen-free Hartley guinea p...Objective To evaluate effect of Neurokinin receptor antagonist on the prevention from hyper-pnea-induced bronchoconstriction using a dual Neurokinin receptor antagonist FK224. Methods 12 pathogen-free Hartley guinea pigs were divided into two groups randomly-. Dimethyl sulfoxide (DMSO) control group (n =6)and FK224 group (n =6). Guinea pigs were anesthetized with pentobarbital sodium. A cervical tracheostomy wasperformed and a polyethylene tube was inserted into the trachea. After measuring baseline value of the lung resist-ance (RL) and dynamic compliance of respiratory system (Cdyn), DMSO (0.3 ml/kg) and FK224 (1mg/kg) wereadministered by injection through jugular vein respectively. A rodent respirator with dry 5% CO2-95% O2 mixture atroom temperature provided mechanical ventilation ( VT 8ml/animal, 100breaths/min) for 5min. RL and Cdyn of 2groups were measured after isocapnic hyperpnea challenge. Results In DMSO control group, isocapnic hyper-pnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of FK224 group did not changesignificantly. Conclusion FK224 can inhibit the increase in RL and decrease in Cdyn caused by isocapnic hy-perpnea in guinea pigs. And antagonists of tachykinins receptors might have effect on prophylaxis and treatment inexercise-induced asthma.展开更多
基金in part has been supported by the Neurosurgical Research Foundation, South Australia, Australia
文摘Parkinson＇s disease （PD） is the most common motor neurode- generative disorder affecting approximately 4 million people worldwide. Although PD presents primarily with motor dysfunction, non-motor symptoms including cognitive decline, mood disorders, reduced olfaction and constipation are also of- ten present, with some of these non-motor symptoms even pre- senting prior to the onset of motor symptoms. It is well known that PD is largely caused by the gradual degeneration of dopa- minergic neurons within the substantia nigra pars compacta （SNc）, along with the presence of protein aggregates called Lewy bodies, which consist primarily of ct-synuclein and are found in the cytoplasm of surviving neurons. This ongoing cell loss and Lewy body pathology is not confined to the SNc, but is also seen in other brain regions implicated in PD pathogenesis such as the locus ceruleus.
文摘The expression of the types of tachykinin receptors in the dorsal root ganglion (DRG) neurons by means of Xenopus oocyte expressing system was studied. Poly(A) +RNAs were extracted from cat cervical and lumbar DRG. Two days after injection of Poly(A) +RNAs, the oocytes were recorded with the two electrode voltage clamp technique. In the oocytes injected with DRG poly(A) +RNA,[Sar 9,Met(O 2) 11 ] substance P(Sar SP, 1 μmol/L), neurokinin A (NKA,1 μmol/L) or [β Ala 8] neurokinin A (4-10) (Ala NKA, 1 μmol/L) produced an inward current comprising a rapid spike and a long sustained oscillatory component for several minutes. Sar SP induced response was blocked by NK 1 antagonist L 668, 169 (1 μmol/L), but not by NK 2 antagonist L 659,877(1μmol/L). In contrast, Ala NKA and NKA responses were only blocked by L 659,877. The oocytes injected with DH Poly(A) +RNA also responded to Sar SP and NKA with similar inward currents, which were selectively blocked by L 668,169 and L 659,877, respectively. These tachykinins induced responses had a potent desensitization. The present data indicate expression of NK 1 and NK 2 receptors in DRG neurons, suggesting that there may be tachykinin autoreceptors on the nociceptive primary afferent terminals.
文摘Objective To evaluate effect of Neurokinin receptor antagonist on the prevention from hyper-pnea-induced bronchoconstriction using a dual Neurokinin receptor antagonist FK224. Methods 12 pathogen-free Hartley guinea pigs were divided into two groups randomly-. Dimethyl sulfoxide (DMSO) control group (n =6)and FK224 group (n =6). Guinea pigs were anesthetized with pentobarbital sodium. A cervical tracheostomy wasperformed and a polyethylene tube was inserted into the trachea. After measuring baseline value of the lung resist-ance (RL) and dynamic compliance of respiratory system (Cdyn), DMSO (0.3 ml/kg) and FK224 (1mg/kg) wereadministered by injection through jugular vein respectively. A rodent respirator with dry 5% CO2-95% O2 mixture atroom temperature provided mechanical ventilation ( VT 8ml/animal, 100breaths/min) for 5min. RL and Cdyn of 2groups were measured after isocapnic hyperpnea challenge. Results In DMSO control group, isocapnic hyper-pnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of FK224 group did not changesignificantly. Conclusion FK224 can inhibit the increase in RL and decrease in Cdyn caused by isocapnic hy-perpnea in guinea pigs. And antagonists of tachykinins receptors might have effect on prophylaxis and treatment inexercise-induced asthma.
