Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physi...Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.展开更多
Therapeutic intervention for spinal cord injury is limited,with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative training.As compared with learning novel com...Therapeutic intervention for spinal cord injury is limited,with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative training.As compared with learning novel compensatory strategies,rehabilitation focuses on resto ring movements lost to injury.Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning,or if it engages previously trained motor circuits without requiring novel learning remains an open question.In this study,mice we re randomly assigned to receive intrape ritoneal injection with the pan-nicotinic,non-competitive antagonist mecamylamine and the nicotinicα7 subunit selective antagonist methyllycaconitine citrate salt or vehicle(normal saline)prior to motor learning assays,then randomly reassigned after motor learning for rehabilitation study post-injury.Ce rvical spinal co rd dorsal column lesion was used as a model of in complete injury.Results of this study showed that nicotinic acetylcholine signaling was required for motor learning of the single pellet-reaching task but it was dispensable for the rehabilitation of the same task after injury.Our findings indicate that critical diffe rences exist between the molecular mechanisms supporting compensatory motor learning strategies and the restoration of behavior lost to spinal cord injury.展开更多
Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury.En...Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury.Endothelial dysfunction can be caused by hypoxia/reoxygenation(H/R)via oxidative stress and metabolic alterations.The present study investigated whether AT3 regulates the production of nitric oxide(NO)and reactive oxygen species(ROS),and the HIF-1αpathway via regulation of muscarinic acetylcholine receptors(mAChRs)in brain microvascular endothelial cells after H/R exposure.Methods:Under H/R conditions,hCMEC/D3 cerebral microvascular endothelial cells were treated with AT3.Specific inhibitors of M2-and M4-mAChRs were used to explore the mechanism by which AT3 influences oxidative stress in endothelial cells.Then,mAChRs expression was detected by western blotting and NO production was detected by Greiss reaction.The intracellular ROS level was measured using DCFH-DA probes.The expression of hypoxia-inducible transcription factor 1α(HIF-1α)was also detected.Results:While H/R induced the expression of M2-and M4-mAChRs,AT3 suppressed the H/R-upregulated M2-and M4-mAChRs.H/R also induced the production of NO,ROS,and apoptosis.AT3 and M4-mAChR inhibitors inhibited the H/R-induced production of NO and ROS and apoptosis.HIF-1αwas induced by H/R,but was suppressed by AT3.Conclusion:Thus,the in vitro evidence shows that AT3 protects against H/R injury in cerebral microvascular endothelial cells via inhibition of HIF-1α,NO and ROS,predominantly through the downregulation of M4-mAChR.The findings offer novel understandings regarding AT3-mediated attenuation of endothelial cell apoptosis and cerebral ischemia/reperfusion injury.展开更多
Nicotinic acetylcholine receptors (nAChRs) play a significant role in excitatory synaptic transmission in insects and are the target for chloronicotinyl and nereistoxin insecticides.In recent years,Chilo suppressalis,...Nicotinic acetylcholine receptors (nAChRs) play a significant role in excitatory synaptic transmission in insects and are the target for chloronicotinyl and nereistoxin insecticides.In recent years,Chilo suppressalis,an economically important pest of rice,developed high resistance against monosultap,a nereistoxin insecticide acting on nAChR.In order to reveal the hypothesized target insensitive mechanism,studies on the molecular property of nAChR from Chilo suppressalis are required.In this study,the full length cDNA of nAChR α subunit from this pest was cloned by RT-PCR.Sequence analysis shows that it is a novel nAChR α subunit,which was named as Cs α 1(Genbank accession No.AF418987).It contains 1?997?bp nucleotides and involves an open reading frame (ORF) encoding a mature protein of 509 amino acids excluding a signal peptide of 24 amino acids.The deduced amino acid sequence was 52%-94% identical to the reported insect nAChR genes.展开更多
Acetylcholine (Ach) is a key component of animal cholinergic system. Recent experiments demonstrated that Ach, choline acetyltransferase, acetylcholinesterase and Ach receptors are present in all parts of plants and...Acetylcholine (Ach) is a key component of animal cholinergic system. Recent experiments demonstrated that Ach, choline acetyltransferase, acetylcholinesterase and Ach receptors are present in all parts of plants and have many functions, including inducing stomatal movement. The authors' previous work has evidenced that microtubules and microfilaments are involved in regulating both stomatal closing and opening. The present investigation is to determine whether stomatal opening induced by Ach is associated with microtubules and microfilaments. The results showed that Ach could induce stomatal opening of Vicia faba L. with or without addition of KCl in the dark. Ach also stimulated protoplast swelling in a K +_free solution in the dark. However, the induction was partially suppressed when the strips and protoplasts were pretreated with either cytochalasin B, an inhibitor of F_actin polymerization, or oryzalin, an inhibitor of plant microtubule polymerization. Thus, our data suggest for the first time that stomatal opening induced by Ach is associated with the dynamics of microtubules and microfilaments.展开更多
Objective This study is to explore the relationship between acetylcholine(ACh)-induced calcium release from intracellular Ca2+ stores and function of outer hair cell(OHC) motors, in an attempt to elucidate the mechani...Objective This study is to explore the relationship between acetylcholine(ACh)-induced calcium release from intracellular Ca2+ stores and function of outer hair cell(OHC) motors, in an attempt to elucidate the mechanism of OHC electromotility at resting state. Methods OHCs were isolated from adult guinea pig (200-300 g) cochlea and loaded with Fluo-3/AM. The cells were treated with ACh/dHBSS, ACh/HBSS, dHBSS only or HBSS only. Intracellular [Ca2+]i variations in cells under the four treatments were observed using an Ar-Kr laser scan confocal microscope. Results [Ca2+]i oscillations were recorded in five OHCs treated with ACh/dHBSS but not in other cells. This is the first time that Ach-excited [Ca2+]i oscillations are reported in guinea pig OHCs independent of extracellular calcium. Conclusions ACh-excited [Ca2+]i oscillations in OHCs originates from intracellular calcium release and may play a crucial role in maintaining active mechanical motility of the OHC at resting and modulating OHC electromotility.展开更多
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el...During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.展开更多
非痴呆型血管性认知障碍(vascular cognitive impairment no dementia,VCIND)是认知障碍的早期阶段,认知损害尚未达到痴呆的标准。本文从中医“虚、痰、瘀”的病因病机进行阐述,脾肾亏虚为发病基础,痰瘀互结为致病因素,导致髓海不足,清...非痴呆型血管性认知障碍(vascular cognitive impairment no dementia,VCIND)是认知障碍的早期阶段,认知损害尚未达到痴呆的标准。本文从中医“虚、痰、瘀”的病因病机进行阐述,脾肾亏虚为发病基础,痰瘀互结为致病因素,导致髓海不足,清窍失养,发为痴呆。胆碱能通路与认知障碍的发生发展密切相关,包括神经递质乙酰胆碱的缺乏、脑白质病变影响胆碱能通路的网络连接以及胆碱能抗炎通路等。探讨中医虚痰瘀的病机演变与胆碱能通路发病机制之间的关系,有助于进一步发掘中医中药治疗在胆碱能通路的作用。展开更多
BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their occurrence.AIM To investigate whether coronary spasms can be predicted using changes i...BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their occurrence.AIM To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the SPT.METHODS Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery pressure.During each SPT,the pressure wire was advanced into the distal portion of the right coronary artery(RCA)and left anterior descending coronary artery,and the ratio of intracoronary pressure to aortic pressure(Pd/Pa)was monitored.Coronary spasm was defined as an arterial narrowing of>90%in response to the administration of acetylcholine(ACh),with chest symptoms and/or ischemic electrocardiographic changes.ACh was administered to the RCA at low,moderate,or high doses of 20,50,or 80μg,respectively,and to the left coronary artery(LCA)at low,moderate,or high doses of 50,100,or 200μg,respectively.Coronary arteries with coronary spasms at low doses of ACh were defined as group L,and those with coronary spasms at moderate or high doses were defined as group MH.Those who did not occur coronary spasms at any ACh dose were designated as group N.RESULTS Among the 132 coronary arteries assessed using a pressure wire,there were 49 in group N,25 in group L,and 58 in group MH.Baseline Pd/Pa was the lowest in group L(P=0.001).The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N(P<0.001).A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95,with a sensitivity of 0.600(15/25)and a specificity of 0.713(76/107)and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was−0.04,with a sensitivity of 0.741(43/58)and a specificity of 0.694(34/49).CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for predicting the occurrence of coronary spasms.展开更多
Objective To examine the effect of acetylcholine（ACh）on the electric activities of pain-excitation neurons （PEN）and pain-inhibitation neurons（PIN）in the hippocampal CA1 area of normal rats or morphinistic rats,a...Objective To examine the effect of acetylcholine（ACh）on the electric activities of pain-excitation neurons （PEN）and pain-inhibitation neurons（PIN）in the hippocampal CA1 area of normal rats or morphinistic rats,and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.Methods The trains of electric impulses applied to sciatic nerve were set as noxious stimulation.The discharges of PEN and PIN in the CA l area were recorded extracellularly by glass microelectrode.We observed the influence of intracerebroventricular （i.c.v.）injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.Results Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats.In normal rats,ACh decrease the pain-evoked discharge frequency of PEN,while increased the frequency of PIN.These effects reached the peak value at 4 min after injection of ACh.In morphinistic rats,ACh also inhibited the PEN electric activity and potentialized the PIN electric activity,but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.Conclusion Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation.Morphine addiction attenuated the sensitivity of painrelated neurons to the noxious information.展开更多
基金National Natural Science Foundation of China(32202800)Natural Science Foundation of Heilongjiang Province(LH2022C104)+1 种基金Heilongjiang Province Education Department Fundamental Scientifc Research Funds(145109516)Qiqihar University Graduate Innovative Research Project(YJSCX2022016).
文摘Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.
基金supported by the Burke Foundation and the National Institutes of Health Common Fund,No.DP2 NS106663(to ERH)the New York State Department of Health Spinal Cord Injury Research Board Postdoctoral Fellowship,No.C32633GG(to YL)。
文摘Therapeutic intervention for spinal cord injury is limited,with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative training.As compared with learning novel compensatory strategies,rehabilitation focuses on resto ring movements lost to injury.Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning,or if it engages previously trained motor circuits without requiring novel learning remains an open question.In this study,mice we re randomly assigned to receive intrape ritoneal injection with the pan-nicotinic,non-competitive antagonist mecamylamine and the nicotinicα7 subunit selective antagonist methyllycaconitine citrate salt or vehicle(normal saline)prior to motor learning assays,then randomly reassigned after motor learning for rehabilitation study post-injury.Ce rvical spinal co rd dorsal column lesion was used as a model of in complete injury.Results of this study showed that nicotinic acetylcholine signaling was required for motor learning of the single pellet-reaching task but it was dispensable for the rehabilitation of the same task after injury.Our findings indicate that critical diffe rences exist between the molecular mechanisms supporting compensatory motor learning strategies and the restoration of behavior lost to spinal cord injury.
基金funding from the National Natural Science Foundation of China(12272246)the Key Research and Development Projects of Sichuan Province(2023YFS0075).
文摘Background:Anisodine hydrobromide(AT3),an anti-cholinergic agent,could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury.Endothelial dysfunction can be caused by hypoxia/reoxygenation(H/R)via oxidative stress and metabolic alterations.The present study investigated whether AT3 regulates the production of nitric oxide(NO)and reactive oxygen species(ROS),and the HIF-1αpathway via regulation of muscarinic acetylcholine receptors(mAChRs)in brain microvascular endothelial cells after H/R exposure.Methods:Under H/R conditions,hCMEC/D3 cerebral microvascular endothelial cells were treated with AT3.Specific inhibitors of M2-and M4-mAChRs were used to explore the mechanism by which AT3 influences oxidative stress in endothelial cells.Then,mAChRs expression was detected by western blotting and NO production was detected by Greiss reaction.The intracellular ROS level was measured using DCFH-DA probes.The expression of hypoxia-inducible transcription factor 1α(HIF-1α)was also detected.Results:While H/R induced the expression of M2-and M4-mAChRs,AT3 suppressed the H/R-upregulated M2-and M4-mAChRs.H/R also induced the production of NO,ROS,and apoptosis.AT3 and M4-mAChR inhibitors inhibited the H/R-induced production of NO and ROS and apoptosis.HIF-1αwas induced by H/R,but was suppressed by AT3.Conclusion:Thus,the in vitro evidence shows that AT3 protects against H/R injury in cerebral microvascular endothelial cells via inhibition of HIF-1α,NO and ROS,predominantly through the downregulation of M4-mAChR.The findings offer novel understandings regarding AT3-mediated attenuation of endothelial cell apoptosis and cerebral ischemia/reperfusion injury.
文摘Nicotinic acetylcholine receptors (nAChRs) play a significant role in excitatory synaptic transmission in insects and are the target for chloronicotinyl and nereistoxin insecticides.In recent years,Chilo suppressalis,an economically important pest of rice,developed high resistance against monosultap,a nereistoxin insecticide acting on nAChR.In order to reveal the hypothesized target insensitive mechanism,studies on the molecular property of nAChR from Chilo suppressalis are required.In this study,the full length cDNA of nAChR α subunit from this pest was cloned by RT-PCR.Sequence analysis shows that it is a novel nAChR α subunit,which was named as Cs α 1(Genbank accession No.AF418987).It contains 1?997?bp nucleotides and involves an open reading frame (ORF) encoding a mature protein of 509 amino acids excluding a signal peptide of 24 amino acids.The deduced amino acid sequence was 52%-94% identical to the reported insect nAChR genes.
文摘Acetylcholine (Ach) is a key component of animal cholinergic system. Recent experiments demonstrated that Ach, choline acetyltransferase, acetylcholinesterase and Ach receptors are present in all parts of plants and have many functions, including inducing stomatal movement. The authors' previous work has evidenced that microtubules and microfilaments are involved in regulating both stomatal closing and opening. The present investigation is to determine whether stomatal opening induced by Ach is associated with microtubules and microfilaments. The results showed that Ach could induce stomatal opening of Vicia faba L. with or without addition of KCl in the dark. Ach also stimulated protoplast swelling in a K +_free solution in the dark. However, the induction was partially suppressed when the strips and protoplasts were pretreated with either cytochalasin B, an inhibitor of F_actin polymerization, or oryzalin, an inhibitor of plant microtubule polymerization. Thus, our data suggest for the first time that stomatal opening induced by Ach is associated with the dynamics of microtubules and microfilaments.
文摘Objective This study is to explore the relationship between acetylcholine(ACh)-induced calcium release from intracellular Ca2+ stores and function of outer hair cell(OHC) motors, in an attempt to elucidate the mechanism of OHC electromotility at resting state. Methods OHCs were isolated from adult guinea pig (200-300 g) cochlea and loaded with Fluo-3/AM. The cells were treated with ACh/dHBSS, ACh/HBSS, dHBSS only or HBSS only. Intracellular [Ca2+]i variations in cells under the four treatments were observed using an Ar-Kr laser scan confocal microscope. Results [Ca2+]i oscillations were recorded in five OHCs treated with ACh/dHBSS but not in other cells. This is the first time that Ach-excited [Ca2+]i oscillations are reported in guinea pig OHCs independent of extracellular calcium. Conclusions ACh-excited [Ca2+]i oscillations in OHCs originates from intracellular calcium release and may play a crucial role in maintaining active mechanical motility of the OHC at resting and modulating OHC electromotility.
基金supported by Catalan Government,Nos.2014SGR344(to JT),2017SGR704(to JT),2021SGR01214(to MAL)MCIN/AEI/10.13039/501100011033/by“ERDF A way of making Europe,”Nos.SAF2015-67143(to JT),PID2019-106332GB-I00(to JT and MAL)and PID2022-141252NB-I00(to MAL).
文摘During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.
文摘非痴呆型血管性认知障碍(vascular cognitive impairment no dementia,VCIND)是认知障碍的早期阶段,认知损害尚未达到痴呆的标准。本文从中医“虚、痰、瘀”的病因病机进行阐述,脾肾亏虚为发病基础,痰瘀互结为致病因素,导致髓海不足,清窍失养,发为痴呆。胆碱能通路与认知障碍的发生发展密切相关,包括神经递质乙酰胆碱的缺乏、脑白质病变影响胆碱能通路的网络连接以及胆碱能抗炎通路等。探讨中医虚痰瘀的病机演变与胆碱能通路发病机制之间的关系,有助于进一步发掘中医中药治疗在胆碱能通路的作用。
文摘BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their occurrence.AIM To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the SPT.METHODS Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery pressure.During each SPT,the pressure wire was advanced into the distal portion of the right coronary artery(RCA)and left anterior descending coronary artery,and the ratio of intracoronary pressure to aortic pressure(Pd/Pa)was monitored.Coronary spasm was defined as an arterial narrowing of>90%in response to the administration of acetylcholine(ACh),with chest symptoms and/or ischemic electrocardiographic changes.ACh was administered to the RCA at low,moderate,or high doses of 20,50,or 80μg,respectively,and to the left coronary artery(LCA)at low,moderate,or high doses of 50,100,or 200μg,respectively.Coronary arteries with coronary spasms at low doses of ACh were defined as group L,and those with coronary spasms at moderate or high doses were defined as group MH.Those who did not occur coronary spasms at any ACh dose were designated as group N.RESULTS Among the 132 coronary arteries assessed using a pressure wire,there were 49 in group N,25 in group L,and 58 in group MH.Baseline Pd/Pa was the lowest in group L(P=0.001).The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N(P<0.001).A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95,with a sensitivity of 0.600(15/25)and a specificity of 0.713(76/107)and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was−0.04,with a sensitivity of 0.741(43/58)and a specificity of 0.694(34/49).CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for predicting the occurrence of coronary spasms.
基金the National Natural Science Foundation of China（No.30240058）.
文摘Objective To examine the effect of acetylcholine（ACh）on the electric activities of pain-excitation neurons （PEN）and pain-inhibitation neurons（PIN）in the hippocampal CA1 area of normal rats or morphinistic rats,and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.Methods The trains of electric impulses applied to sciatic nerve were set as noxious stimulation.The discharges of PEN and PIN in the CA l area were recorded extracellularly by glass microelectrode.We observed the influence of intracerebroventricular （i.c.v.）injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.Results Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats.In normal rats,ACh decrease the pain-evoked discharge frequency of PEN,while increased the frequency of PIN.These effects reached the peak value at 4 min after injection of ACh.In morphinistic rats,ACh also inhibited the PEN electric activity and potentialized the PIN electric activity,but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.Conclusion Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation.Morphine addiction attenuated the sensitivity of painrelated neurons to the noxious information.
