AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were...AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments.Gastric blood flow was measured by laser-Doppler flow-metry. RESULTS: ET-3 and an ETB receptor antagonist sig- nificantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Cap-saicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET B receptor and by sensory afferent neurons.展开更多
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
A new frog skin peptide, ranamargarin depicted as H-Asp-Asp-Ala-Ser-Asp-Arg-Ala-Lys-Lys-Phe-Tyr-Gly-Leu-Met-NH<sub>2′</sub>, was synthesized by the conventionalmethod. Comparisons of chemical and biologic...A new frog skin peptide, ranamargarin depicted as H-Asp-Asp-Ala-Ser-Asp-Arg-Ala-Lys-Lys-Phe-Tyr-Gly-Leu-Met-NH<sub>2′</sub>, was synthesized by the conventionalmethod. Comparisons of chemical and biological properties of both the synthetic and natural ranamargarins indicated that they were identical, so the chemical structure of ranamargarin was confirmed. Preliminary pharmacological study showed that ranamargarin was highly selective towards the SP-P subtype receptor.展开更多
基金Supported by A fellowship from Fundaao de Amparo a Pes-quisa do Estado de Sao Paulo, FAPESP, Brazil (to Cmara PRS)a research grant from FAPESP (to Ferraz JGP)
文摘AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments.Gastric blood flow was measured by laser-Doppler flow-metry. RESULTS: ET-3 and an ETB receptor antagonist sig- nificantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Cap-saicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET B receptor and by sensory afferent neurons.
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.
基金Project supported by the National Natural Science Foundation of China.
文摘A new frog skin peptide, ranamargarin depicted as H-Asp-Asp-Ala-Ser-Asp-Arg-Ala-Lys-Lys-Phe-Tyr-Gly-Leu-Met-NH<sub>2′</sub>, was synthesized by the conventionalmethod. Comparisons of chemical and biological properties of both the synthetic and natural ranamargarins indicated that they were identical, so the chemical structure of ranamargarin was confirmed. Preliminary pharmacological study showed that ranamargarin was highly selective towards the SP-P subtype receptor.
