Biomedical subjects

K C Chang

Publications and source records attributed to K C Chang.

At least 37 records · Page 2Linked to original sources

PubMed2001

Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans.

Patients with sepsis have impaired host defenses that contribute to the lethality of the disorder. Recent work implicates lymphocyte apoptosis as a potential factor in the immunosuppression of sepsis. If lymphocyte apoptosis is an important mechanism, specific subsets of lymphocytes may be more vulnerable. A prospective study of lymphocyte cell typing and apoptosis was conducted in spleens from 27 patients with sepsis and 25 patients with trauma. Spleens from 16 critically ill nonseptic (3 prospective and 13 retrospective) patients were also evaluated. Immunohistochemical staining showed a caspase-9-mediated profound progressive loss of B and CD4 T helper cells in sepsis. Interestingly, sepsis did not decrease CD8 T or NK cells. Although there was no overall effect on lymphocytes from critically ill nonseptic patients (considered as a group), certain individual patients did exhibit significant loss of B and CD4 T cells. The loss of B and CD4 T cells in sepsis is especially significant because it occurs during life-threatening infection, a state in which massive lymphocyte clonal expansion should exist. Mitochondria-dependent lymphocyte apoptosis may contribute to the immunosuppression in sepsis by decreasing the number of immune effector cells. Similar loss of lymphocytes may be occurring in critically ill patients with other disorders.

Adolescent↗

PubMed2001

Hypotensive effects of captopril on physical properties of the arterial system in young and adult rats.

We determined the acute effects of the angiotension converting enzyme inhibitor captopril on the arterial mechanics in rats at different ages, based on the exponentially tapered T-tube model. Male Wistar-Kyoto rats aged 4 and 12 months were individually referred to as young (n = 8) and adult rats (n = 8) and were anesthetized and thoractomized. The pulsatile aortic pressure and flow signals before and after the administration of captopril (20 mg/kg, i.p.) were measured by a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. In each age group, captopril showed little change in basal heart rate as well as cardiac output. However, captopril produced a drop of 15% in mean aortic pressure in young and a fall of 12% in adult rats. In addition. captopril reduced total peripheral resistance by 21% in young and by 23% in adult animals. As for the pulsatile nature of the arterial system, captopril had increased wave transit time of the lower body circulation of 10% in young and of 12% in adult rats. By contrast, captopril reduced wave reflection factor by 22% in young and by 25% in adult animals. In conclusion, the converting enzyme inhibitor captopril has a stiffness-decreasing effect on Windkessel vessels and a dilated effect on resistance arterioles in either young or adult rats. No age dependence of vascular response and reflex tachycardia to captopril has been found in rats between 4 and 12 months.

Aging↗

PubMed2001

Molecular and quantitative characterisation of the porcine embryonic myosin heavy chain gene.

The porcine embryonic myosin heavy chain (MyHC) is a major isoform in foetal skeletal muscle, and is the last remaining major porcine skeletal MyHC gene to be isolated and characterised. We report here on its cDNA and genomic isolation, molecular characterisation, quantification and expression. Unlike all other porcine and mammalian skeletal MyHC genes reported to date, the deduced translated start site of the porcine embryonic gene was located in exon 2, instead of exon 3. Its promoter conferred differentiation-specific expression. We found, by quantitative real-time RT-PCR, that for much of gestation the embryonic MyHC was by far the most transcriptionally active gene compared with the slow/I and perinatal MyHC isoforms, and it was consistently more highly expressed than the perinatal isoform throughout gestation. The embryonic MyHC isoform was, however, rapidly down-regulated at around birth. By contrast, 22 weeks after birth, the porcine perinatal isoform remained detectable by PCR. Additionally, we discovered the presence of differential splicing at the 3'-end of the embryonic MyHC gene that resulted in an in-frame deletion, with the consequential loss of 93 amino acids close to the ACD domain, a region that is important for the assembly of myosin filaments. The detection of this truncated variant points to a possible major post-transcriptional mechanism of embryonic MyHC regulation that may be linked to myosin filament formation or turnover.

Alternative Splicing↗

PubMed2001

Mechanical effects of liriodenine on the left ventricular-arterial coupling in Wistar rats: pressure-stroke volume analysis.

1. In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identified as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10(-7) g kg(-1). The aim of this study was to determine whether liriodenine at its effective anti-arrhythmic dose of 10(-7) g kg(-1) had effects on the left ventricular (LV)-arterial coupling in Wistar rats. 2. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E(es)) and effective arterial volume elastance (E(a)), respectively. The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the optimality of energy transmission from the left ventricle to the arterial system. 3. Liriodenine at the dose of 10(-7) g kg(-1) showed no significant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (P(es)), E(a), E(es), and Q(load). 4. By contrast, liriodenine at the dose of 10(-6) g kg(-1) produced a significant fall of 2.0% in HR and a significant rise of 5.8% in CO, but no significant change in P(es). Moreover, liriodenine administration of 10(-6) g kg(-1) to rats significantly decreased E(es) by 8.5% and E(a) by 10.6%, but did not change Q(load). 5. We conclude that liriodenine at the dose of 10(-7) g kg(-1) has no effects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the effective anti-arrhythmic dose, liriodenine shows no effects on the efficiency of energy transferred from the left ventricle to the arterial system.

Analysis of Variance↗

PubMed2001

Vascular dysfunction induced by AGE is mediated by VEGF via mechanisms involving reactive oxygen species, guanylate cyclase, and protein kinase C.

OBJECTIVE: These experiments were designed to elucidate mechanisms mediating vascular dysfunction induced by advanced glycation end products (AGEs). METHODS: Skin chambers were mounted on the backs of Sprague-Dawley rats and 1 week later, granulation tissue that formed in the bottom of the chamber was exposed twice daily for 7 days to glycated rat serum albumin in the presence and absence of inhibitors of reactive oxygen intermediates, nitric oxide synthase and guanylate cyclase, protein kinase C (PKC), and a neutralizing vascular endothelial growth factor (VEGF) antibody. Vascular (125)I-albumin clearance and blood flow were quantified by use of a double isotope-dilution technique and radiolabeled microspheres, respectively. RESULTS: Albumin permeation and blood flow were increased dose-dependently to a maximum of 2 to 3 times controls by increasing the extent of glucose modification, the concentration, or the duration of exposure to glycated albumin. These increases were significantly attenuated by probucol and superoxide dismutase; N(G)-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase inhibitor; LY83583, a guanylate cyclase inhibitor; and LY333531, a beta-isoform-selective protein kinase C inhibitor. A neutralizing VEGF monoclonal antibody also markedly attenuated the permeability and blood flow increases induced by glycated albumin. CONCLUSIONS: These observations indicate potentially important roles for oxygen free-radicals and nitric oxide in mediating permeability and blood flow changes induced by glycated proteins via mechanisms involving increased protein kinase C activity and VEGF production. Striking similarities in the mechanism by which hyperglycemia and glycated proteins induce vascular dysfunction suggest that a common pathway mediates effects of these different metabolic imbalances on vascular dysfunction.

Animals↗

PubMed2001

Follicular dendritic cell sarcoma of the colon mimicking stromal tumour.

AIMS: Follicular dendritic cell tumours are very rare neoplasms that often occur in lymph nodes. We report here a case in the colon, a hitherto unreported site, in a 37-year-old female. The differentiation from gastrointestinal stromal tumour is emphasized. METHODS AND RESULTS: The tumour was tan, elastic and solid with surface ulceration. Microscopically, it was composed of oval to spindle tumour cells with syncytial cytoplasm arranged in fascicular and whorled patterns. There were many infiltrating lymphocytes. The histological appearance resembled gastrointestinal stromal tumour, thymoma or meningioma. Distinct from the stromal tumour, the lymph node was also involved by the tumour. Immunohistochemically, the tumour cells were positive for CD21, CD35 and CD68, but negative for cytokeratin, CD34, smooth muscle actin, desmin, S100 protein, epithelial membrane antigen, leukocyte common antigen, HMB-45 and c-kit. In-situ hybridization study was negative for Epstein-Barr virus RNA sequences. Ultrastructurally, the tumour cells possessed cytoplasmic processes joined by desmosomes. CONCLUSIONS: This entity should be considered in the list of differential diagnoses for gastrointestinal stromal tumour. The lymph node metastasis and immunohistochemical features are of value for identification of this rare neoplasm.

Adult↗

PubMed2001

Anti-thrombotic effects of higenamine.

The anti-platelet and anti-thrombotic effects of higenamine, a benzyltetrahydroisoquinoline alkaloid of the roots of Aconitum japonicum (Ranunculaceae), were investigated. The degree of platelet aggregation was measured with platelet rich plasma (PRP). An acute thrombotic condition was induced in mice by the injection of the mixture of collagen and epinephrine. The thrombus formation was induced inside the arterio-venous shunt tube installed between an abdominal aorta and the renal vein of rats. Higenamine showed inhibitory activities to both human and rat platelet aggregation induced by ADP, collagen and epinephrine. It was more inhibitory to epinephrine induced aggregation (IC(50); 19 and 7.2 microM to human and rat platelets respectively) than ADP- or collagen-induced aggregation. The anti-thrombotic effects of higenamine were also observed in both mouse acute thrombosis model and rat arterio-venous shunt (AV-shunt) models. The oral administration of higenamine (50 or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV-shunt tube in rats.

Alkaloids↗

PubMed2001

Effects of food restriction on systolic mechanical behavior of the ventricular pump in middle-aged and senescent rats.

Previous work from our laboratory has revealed that the intrinsic contractility of the left ventricle is depressed in rats at 24 months, and the ventricular internal resistance shows declines with age. The aim of this study was to determine whether food restriction (FR) delays the development of age-related changes in left ventricular (LV) contractility and internal resistance. Male Fischer 344 rats that began FR at the ages of 12 and 18 months were fed on alternate days for 6 months and compared with age-matched ad libitum (AL)-fed rats. Rats studied at the ages of 18 and 24 months were referred to as middle-aged and senescent rats, respectively, and were anesthetized and thoracotomized. We measured LV pressure and ascending aortic flow waves by using a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. The elastance-resistance model was used to generate Emax and Qmax to describe the physical properties of the left ventricle; Emax is the maximal systolic elastance to represent the myocardial contractility; Qmax is the theoretical maximal flow to be inversely related to the LV internal resistance. Neither age nor diet affected basal heart rate, LV end-systolic pressure, or cardiac output. Emax normalized to LV weight (Emaxn) exhibited a decline from 941.9+/-62.7 mmHg/ml-g to 690.2+/-57.5 mmHg/ml-g with age in AL-fed rats but not FR rats. Qmax showed an increase with age from 36.55+/-2.78 ml/s to 44.22+/-2.62 ml/s in AL-fed rats or from 36.01+/-2.09 ml/s to 43.52+/-2.74 ml/s in FR rats. There was no effect of diet on Qmax. In conclusion, FR prevents or delays the reduction in myocardial contractility that occurred between 18 and 24 months of age in AL rats. However, FR does not affect the age-related changes in ventricular internal resistance.

Aging↗

PubMed2001

Lack of relation between severity of stroke and severity of extracranial internal carotid artery lesions in Taiwanese first-ever ischemic stroke patients.

BACKGROUND AND PURPOSE: The authors attempt to determine whether hemodynamically significant extracranial internal carotid artery (ICA) lesions correlate with the severity of first-ever hemispheric ischemic stroke. METHODS: Carotid duplex was used to evaluate carotid arteries. The National Institutes of Health Stroke Scale was used to describe the severity of the stroke and was stratified as follows: 1-6 = mild, 7-15 = moderate, > 15 = severe. Duplex findings were categorized according to velocity criteria into < 50% stenosis if ICA peak systolic velocity (PSV) (cm/s) < 140 and > 50% stenosis if ICA PSV > 140 or ratio of ICA and common carotid artery in PSV > 2. No detectable flow at ICA was considered occlusion. Stroke subtype was classified according to TOAST criteria. RESULTS: Two hundred nineteen consecutive patients were enrolled, including 127 with mild, 65 with moderate, and 27 with severe stroke. The prevalence of ICA stenosis > 50% in each group was 3.6%, 1.4%, 0.9%, respectively. Two patients in the severe group had total ICA occlusion. The overall prevalence of significant ICA lesions was 6.8%. CONCLUSIONS: There is no positive correlation of stroke severity with the severity of duplex findings, which may be due to low prevalence of significant ICA lesions or other stroke mechanisms. Most of the patients had mild stroke, and the majority had ICA stenosis < 50%. Small-vessel occlusion tended to have mild severity of stroke. Intracranial artery lesions or other factors causing stroke in Taiwanese should be investigated. Given the low incidence of significant extracranial carotid disease in symptomatic Taiwanese stroke patients, routine screening of symptomatic Taiwanese for extracranial carotid artery disease does not provide enough information to determine stroke mechanism, and transcranial Doppler should be added to the screening tests.

Acute Disease↗

PubMed2001

Electrophysiological characteristics and radiofrequency ablation of focal atrial tachycardia originating from the superior vena cava.

The initiation of focal atrial tachycardia (AT) from the superior vena cava (SVC) remains unclear. In 3 patients (2 females, 1 male; aged 57, 66 and 50 years, respectively) with focal AT arising from different parts of the SVC, the AT occurred spontaneously, rather than being induced by electrical stimulation. The cycle length of the tachycardia was highly variable, ranging between 190 and 300 ms in patient 1, 180 and 320ms in patient 2, and 200 and 300ms in patient 3. The clinical or associated arrhythmias were atrial fibrillation (AF) (patients 1, 3) and atrial flutter (AFL) (patients 2, 3). A presumed SVC potential that was earlier than the activation of all the other mapping sites was recorded during AT at the lower anterior (15-mm above the atriocaval junction), the mid-anterior (25-mm above the atriocaval junction) and the lower posterior aspect of the SVC (17-mm above the atriocaval junction. Radiofrequency (RF) ablation targeting the SVC focus with the SVC potential promptly eliminated the focal AT in all 3 patients. The coexistent typical AFL was ablated, but the AF was not. The follow-up period was 6, 6, and 3 months, respectively, for each of the patients under no antiarrhythmic medication; there has not been a recurrence of symptomatic palpitation. In conclusion, focal electrical firing in the SVC can initiate AT and this type of focal AT is always associated with AFL or AF. RF ablation guided by the presumed SVC potential is safe and highly effective in eliminating the tachycardia.

Aged↗

PubMed2001

Tuberculosis risk factors in a silicotic cohort in Hong Kong.

SETTING: Hong Kong silicotic patients are followed regularly at the Pneumoconiosis Clinic. OBJECTIVE: To quantify the incidence of tuberculosis disease that occurs after the date of diagnosis of silicosis (DOD), and to identify the risk factors for its development. DESIGN: Retrospective analysis of a Hong Kong silicotic cohort with DOD from 1 January 1988 to 31 December 1993. RESULTS: Of 718 subjects whose records were identified, 11 were excluded from the study. The incidence of tuberculosis (TB) after DOD was 3019 patients per 100,000 population, approximately nine times that of the local population matched for age and sex. Twelve factors were subject to univariate analysis followed by logistic regression. Four TB risk factors were identified: 1) no anti-tuberculosis treatment before DOD (relative risk [RR] 4.51, 95% confidence interval [CI] 2.46-8.24), 2) progressive massive fibrosis (PMF) (RR 3.78, 95%CI 2.25-6.36), 3) small opacities exceeding 1.5 mm (RR 2.17, 95%CI 1.38-3.42), and 4) caisson work (RR 1.56, 95%CI 1.01-2.41). Relative risks were calculated for patient subgroups stratified according to TB risk factors. CONCLUSION: This study has reaffirmed the strong association of tuberculosis and silicosis, and has identified several TB risk factors with a logistic regression model.

Adult↗

PubMed2001

Nasal glioma: a case report.

Nasal gliomas are rare, benign, congenital tumors that are thought to be the result of an abnormality in embryonic development. Three types of clinical presentations have been recognized: extranasal (60%), intranasal (30%), and combined (10%). Clinically, these masses are firm, noncompressible, nonpulsatile, gray or purple lesions that obstruct the nasal cavity intranasally and cause deformity extranasally. Histologically, these tumors are made up of astrocytic neuroglial cells interlaced with fibrous and vascular connective tissue that is covered with skin or nasal respiratory mucosa. The preferred treatment is excision via a frontal craniotomy approach for those patients whose gliomas have an intracranial connection, for those patients who have cerebrospinal fluid rhinorrhea, and for those who have recurrent episodes of meningitis. Otherwise, a transfacial lateral rhinotomy is advised. In this article, we describe a case of a nasal glioma that was removed via a lateral rhinotomy.

Biopsy, Needle↗

PubMed2001

Efficacy of the BCG revaccination programme in a cohort given BCG vaccination at birth in Hong Kong.

SETTING: Revaccination of tuberculin-negative school-children is a regular practice in Hong Kong. OBJECTIVE: To assess the efficacy of BCG revaccination guided by tuberculin skin testing. METHOD: A cohort of 303,692 children vaccinated at birth was followed through the tuberculosis notification register for the development of active disease. The percentage of cohort who participated in the BCG revaccination program during primary school was estimated from the vaccination statistics of the Hong Kong Department of Health. The BCG revaccination history of identified cases was ascertained through vaccination cards and clinic records. RESULTS: A total of 85.2% of the cohort participated in the BCG revaccination programme; 79.7% of the participants were tuberculin-negative and revaccinated; 343 developed tuberculosis after the age of 11; 302 were among the participants in the programme while 41 were not. The tuberculosis incidence was 16.5 and 12.9 per 100,000 person-years for participants and non-participants, respectively (RR 1.28, 95%CI 0.92-1.77). Among the participants, tuberculosis incidence was 12.5 and 32.0/100,000 person-years, respectively, for the tuberculin-negative/BCG revaccinated group and the tuberculin-positive/non-revaccinated group (RR 0.39, 95%CI 0.31-0.49). CONCLUSION: This study failed to demonstrate any significant difference in the incidence rates of tuberculosis among participants and non-participants in a school BCG revaccination programme. The increased risk for tuberculosis in the tuberculin-positive group does not support the use of the tuberculin testing for detection of immunity conferred by neonatal BCG vaccination.

Adolescent↗

PubMed2001

Clinicopathological report of Candida granuloma from an endogenous candidal endophthalmitis.

Fluconazole was reported to be an effective alternative to Amphotericin B for candidal endophthalmitis. However, the dose for systemic use had not been determined and few pathological reports on its use have been published. An epiretinal membrane harvested from a regressed candidal endophthalmitis in a patient treated with fluconazole (200 mg/day) was sent for pathologic study. On the inner side of the retina, a granuloma was found. Fungal debris was found within the center of the granuloma, but an intact fungus was seen next to the granuloma. Pathologic study showed incomplete treatment in this case, although systemic status had improved. The use of systemic fluconazole should be maintained for a longer period of time to treat candidal endophthalmitis.

Amphotericin B↗

PubMed2000

The state diagram for cell adhesion under flow: leukocyte rolling and firm adhesion.

Leukocyte adhesion under flow in the microvasculature is mediated by binding between cell surface receptors and complementary ligands expressed on the surface of the endothelium. Leukocytes adhere to endothelium in a two-step mechanism: rolling (primarily mediated by selectins) followed by firm adhesion (primarily mediated by integrins). Using a computational method called "Adhesive Dynamics," we have simulated the adhesion of a cell to a surface in flow, and elucidated the relationship between receptor-ligand functional properties and the dynamics of adhesion. We express this relationship in a state diagram, a one-to-one map between the biophysical properties of adhesion molecules and various adhesive behaviors. Behaviors that are observed in simulations include firm adhesion, transient adhesion (rolling), and no adhesion. We varied the dissociative properties, association rate, bond elasticity, and shear rate and found that the unstressed dissociation rate, k(r)(o), and the bond interaction length, gamma, are the most important molecular properties controlling the dynamics of adhesion. Experimental k(r)(o) and gamma values from the literature for molecules that are known to mediate rolling adhesion fall within the rolling region of the state diagram. We explain why L-selectin-mediated rolling, which has faster k(r)(o) than other selectins, is accompanied by a smaller value for gamma. We also show how changes in association rate, shear rate, and bond elasticity alter the dynamics of adhesion. The state diagram (which must be mapped for each receptor-ligand system) presents a concise and comprehensive means of understanding the relationship between bond functional properties and the dynamics of adhesion mediated by receptor-ligand bonds.

Cell Adhesion↗

PubMed2000

Impaired vascular dynamics in normotensive diabetic rats induced by streptozotocin: tapered T-tube model analysis.

This study is to explore the changes of arterial mechanical properties in streptozotocin (STZ)-diabetic rats, based on the exponentially tapered T-tube model. Rats given STZ 65 mg kg(-1)i.v. are compared with untreated weight- and age-matched controls. A high-fidelity pressure sensor and electromagnetic flow probe measured pulsatile pressure and flow waves in the ascending aorta, respectively. Diabetic rats exhibit isobaric vasodilatation that is characterized by an increase in cardiac output and no significant changes in aortic pressure. Total peripheral resistance of diabetic rats is lower than that of weight- and age-matched controls. Diabetic rats have higher total peripheral compliance (2.86+/-0.70 microl mm Hg(-1)) than do weight- (1.77+/-0.34 microl mm Hg(-1)) and age-matched (1.87+/-0.69 microl mm Hg(-1)) controls. Aortic characteristic impedance is reduced from 0.017+/-0.003 mm Hg min kg ml(-1)in weight- and 0.020+/-0.004 mm Hg min kg ml(-1)in age-matched controls to 0.010+/-0.004 mm Hg min kg ml(-1)in diabetic rats. Moreover, diabetic rats show shorter wave transit time in lower body circulation (17.86+/-1.91 ms) than do weight- (20.45+/-1.91) and age-matched (23.05+/-2.04 ms) controls. Under isobaric vasodilatation, the decreased resistance and increased compliance in peripheral circulation suggest that the contractile dysfunction of the smooth muscle cells may occur in resistance arterioles in diabetes. With unaltered aortic pressure, an impairment in aortic distensibility of STZ-diabetic rats is manifest on the reduced wave transit time rather than on the diminished aortic characteristic impedance.

Animals↗

PubMed2000

p53-dependent and -independent pathways of apoptotic cell death in sepsis.

Sepsis induces extensive apoptosis of lymphocytes, which may be responsible for the profound immune suppression of the disorder. Two potential pathways of sepsis-induced lymphocyte apoptosis, Fas and p53, were investigated. Lymphocyte apoptosis was evaluated 20-22 h after sepsis by annexin V or DNA nick-end labeling. Fas receptor-deficient mice had no protection against sepsis-induced apoptosis in thymocytes or splenocytes. p53 knockout mice (p53-/-) had complete protection against thymocyte apoptosis but, surprisingly, had no protection in splenocytes. p53-/- mice had no improvement in sepsis survival compared with appropriately matched control mice with sepsis. We conclude that both p53-dependent and p53-independent pathways of cell death exist in sepsis. This differential apoptotic response of thymocytes vs splenocytes in p53-/- mice suggests that either the cellular response or the death-inducing signal is cell-type specific in sepsis. The fact that p53-/- lymphocytes of an identical subtype (CD8-CD4+) were protected in thymi but not in spleens indicates that cell susceptibility to apoptosis differs depending upon other unidentified factors.

Animals↗

PubMed2000

Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor.

The action of arecoline on rat locus coeruleus neurons was studied by intracellular recording from the in vitro brain slice preparation. Superfusion of arecoline (0.1-100 microM) caused two dose-related effects, an increased firing rate and, in neurons previously hyperpolarized to a constant potential by passing a steady hyperpolarizing current across the membrane, depolarization. Both effects were associated with a reduction in membrane input resistance. Moreover, the arecoline-induced excitatory effects were antagonized by the muscarinic receptor antagonist, atropine, but not by the nicotinic receptor antagonist, hexamethonium. Methoctramine, a selective M2-muscarinic receptor antagonist, was also effective in reversing the arecoline-induced effects, with a dissociation equilibrium constant of 14.2+/-1.2 nM (n=6). These results therefore suggest that arecoline exerts its excitatory actions by binding to M2-muscarinic receptors on the cell membrane of neurons of the locus coeruleus.

Alzheimer Disease↗