Biomedical subjects

X D Wu

Publications and source records attributed to X D Wu.

At least 37 records · Page 2Linked to original sources

PubMed1996

Intraocular pressure trends in pregnancy and in the third trimester hypertensive patients.

BACKGROUND: Systemic blood pressure is positively related to intraocular pressure. During the third trimester of pregnancy decreased intraocular pressure while increased blood pressure has been reported. After taking into account all those factors that can affect intraocular pressure, the present study investigated whether or not the high blood pressure found in late pregnancy influences the known ocular hypotensive effect of late pregnancy. SUBJECTS AND METHODS: Normotensive subjects in all trimesters of pregnancy and non-pregnant control groups along with third trimester hypertensive subjects were studied. Intraocular pressure was measured with the Goldmann applanation tonometer. RESULTS: In the second and third trimester subjects, the mean intraocular pressure was significantly lower than in the non-pregnant control group. The differences between first and second, first and third, and second and third trimesters of pregnancy were (mean +/- s.d.) -0.5 +/- 1.2 (p < 0.05), -1.5 +/- 1.7 (p < 0.001), and -1.0 +/- 2.1 (p < 0.01) mmHg respectively. The mean difference between third trimester hypertensive and third trimester normotensive pregnant women was 0.53 +/- 1.5 mmHg (p < 0.05). CONCLUSIONS: With advancing pregnancy, intraocular pressure decreases. The mean intraocular pressures of third trimester hypertensive pregnant women were significantly higher from that of third trimester non-hypertensives. Knowledge of the normal level of intraocular pressure in various stages of pregnancy may help glaucoma screeners.

Adult↗

PubMed1996

Effect of seasons upon intraocular pressure in healthy population of China.

Studies have been shown that intraocular pressure (IOP) shows a seasonal variation, but amount of change differs from study to study. The variability in their results may be due to negligence of factors that can affect IOP. Due to differences in environmental conditions of China than other countries, we investigated seasonal variations in IOP of 103 healthy male Chinese of Shanghai. IOP was measured each month over the course of fourteen months with the Goldmann applanation tonometer. The average intraocular pressures in the winter months were higher than those in the spring, summer, and autumn months. The IOP difference between winter and summer months was found to be 1.4 +/- 0.7 mmHg. This study confirms that season influences IOP. As compared to other nations, effect of seasons on IOP seems to be somewhat less pronounced in Chinese. The possible mechanisms, responsible for the seasonal variation of intraocular pressure, are also postulated.

Adult↗

PubMed1996

Magnitude of decrease in intraocular pressure depends upon intensity of exercise.

The present study was planned to investigate the relationship between the magnitude of intraocular pressure (IOP) reduction after short-duration exercise and the intensity, duration and quantity of exercise in healthy subjects. Twenty-five healthy, sedentary male of the same age group, performed exercises at the levels of 80%, 60%, and 40% maximum heart rate (HRmax) for 15 minutes, 80% HRmax for 7.5 minutes, 60% HRmax for 10 minutes, and 40% HRmax for 30 minutes. IOP was measured with the Goldmann applanation tonometer. The IOP reduction at 5 minutes after 15 minutes of exercising at 80% HRmax, 60% HRmax, and 40% HRmax were 4.7 +/- 0.9, 3.5 +/- 0.7, and 0.9 +/- 0.4 mmHg, respectively. At five minutes, after exercising 7.5 minutes at 80% HRmax, 10 minutes at 60% HRmax, and 30 minutes at 40% HRmax, IOP reduced by 4.5 +/- 0.7, 3.3 +/- 0.9, and 2.9 +/- 1.1 mmHg, respectively. This study concludes that intensity of exercise seems responsible for the magnitude of the initial IOP decrease after short-term exercise. Furthermore, it seems that other factors such as duration of exercise or quantity of exercise, blood pressures, body mass index are not related to the amount of the initial fall in IOP.

Adult↗

PubMed1996

Effect of physical fitness on plasma lipids in young Chinese adults.

Epidemiological studies indicate that individuals with more physically demanding occupations or leisure time activities generally have a lower rate of coronary heart disease (CHD) than those that are more sedentary. Physical exercise may alleviate the risk factors of CHD. Previous literature regarding the effects of exercise upon triglycerides and cholesterol is contradictory. This study compares the effects of regular physical exercise on the concentration of plasma lipids of thirty male medical students, ages ranging between 21 and 30 years. The diet of all the subjects was nearly the same during the last four years. The subjects participated in a voluntary program of exercise for ten weeks. The differences between before and after the exercises were found to be -0.13 +/- 0.04, -0.13 +/- 0.08, 0.21 +/- 0.05, -0.10 +/- 0.04, -0.02 +/- 0.01 mmol/L of triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol (mean +/- SEM), respectively. The differences between triglycerides, HDL-cholesterol, and LDL-cholesterol were significant (p < 0.05), meanwhile, the differences between total cholesterol and VLDL-cholesterol were insignificant. The marked increase in maximal O2 uptakes after exercise training of ten weeks indicates a significant improvement in the subjects' physical fitness. Based on the results in this study, we can conclude that daily physical exercise may be an effective inhibitor for cardiovascular diseases in later life, thereby necessitating a strategy for physical activity in young adults.

Adult↗

PubMed1996

Diurnal variation of intraocular pressure in normal and ocular hypertensive subjects of China.

This study evaluated the distribution of Intraocular pressure (IOP) levels in 67 normal and 59 ocular hypertensive (OHT) subjects during the day after placing control on all those factors that can affect IOP. The IOP was measured with the Goldmann applanation tonometer. All the subjects were examined according to standard protocols. Both in the normal and OHT subjects, the peak of mean IOP appeared in the morning when the subjects woke up and the trough of mean IOP occurred between 2 a.m. to 4 a.m. The mean diurnal variation were (mean +/- sem) 2.9 +/- 0.7 and 3.5 +/- 0.7 mmHg in the normal and in OHT subjects, respectively. Ninety-four percent of the normal subjects and sixty-eight percent of the OHT subjects exhibited a similar diurnal behaviour in both eyes. The IOP variation did not correlate with the variations of blood pressure. The diurnal variation of IOP, found in Chinese, is lower than in other nations. The clinical importance of findings that the peaks of IOP occur in the early morning, raised a serious question as to the necessity of extending the diurnal IOP curves beyond the usual working time (JPMA 46:171, 1996).

Adult↗

PubMed1996

Distribution of intraocular pressure among healthy Pakistani.

Because the course of glaucoma is often an insidious one and most cases remain asymptomatic until the visual field has been clearly diminished, the frequency distribution of intraocular pressure (IOP) is important from both an academic and clinical viewpoint. However, diagnostically, glaucoma is a disease suited to a preventive approach. Due to differences in intrinsic constitution, diet and environmental conditions, there is a clear need for well collected population-based IOP data in different countries. In the present study, after controlling for the factors that can effect IOP, we investigated the distribution of intraocular pressure in 7201 healthy subjects of both sexes of Karachi, Pakistan. In both sexes, distribution of IOP slightly skewed towards the higher values. In males and females, 85.1% and 82.2% individuals ranged from 11 to 18 mmHg, 4.3% and 3.2% ranged from 8 to 10 mmHg, 7.1% and 11.2% ranged from 19 to 21 mmHg, respectively. Ocular hypertension (IOP > 21 mmHg) was found in 3.5% males and 3.7% females. Intraocular pressure increased with age in both eyes of both sexes. The averages per decade increase were 0.3 mmHg and 0.5 mmHg in male and female respectively. This study reports that an average per decade increase, women have 0.4 mmHg higher IOP than men. The male-female difference was not statistically significant until the age groups reached 31-40 years, after which the differences became significant. Right and left eyes IOPs were found to be 14.3 +/- 0.17 and 14.4 +/- 0.12 mmHg in male and 14.6 +/- 0.14 and 14.8 +/- 0.15 mmHg in females respectively. This survey shows that mean IOP of Pakistani population is similar to the IOP found in other epidemiologic investigations; the prevalence of ocular hypertension, however, seems to be slightly higher. Knowledge of the normal level of IOP in various age groups of both sexes will help to screen glaucoma.

Adolescent↗

PubMed1996

The effect of physical fitness on intraocular pressure in Chinese medical students.

BACKGROUND: Virtually all the tissues and systems of the human body have been shown to be responsive to programs of exercise. Regarding the relationship between physical fitness and intraocular pressure (IOP), the existing literature is controversial with some associations inconsistent. In one study, IOP values were not dependent upon changes in physical fitness. In contrast to this, another study demonstrated that physical fitness significantly reduces intraocular pressure levels. In recent years it has been noted that intraocular pressure is a dynamic function and is subject to many influences both acutely and over the long term. The variety of results of previous studies may have come from several factors which can affect intraocular pressure. The present study was planned to investigate the effects of physical fitness on intraocular pressure in Chinese medical studies, after elimination of other affecting factors. METHODS: Forty medical students were categorized into control and experimental groups, each consisting of 20 subjects. The experimental group took a supervised exercise program for 10 weeks. Physical fitness was evaluated by measurement of maximum oxygen uptake with a Beckman O2 analyzer. Intraocular pressure was measured with the Goldmann applanation tonometer. RESULTS: After exercise training, the experimental group showed a marked increase in physical fitness. The difference of IOP between the control and experimental groups before exercise conditioning was 0.3 +/- 0.1 mmHg (P > 0.05). After 10 weeks, this difference increased to 1.1 +/- 0.4 mmHg (p < 0.05). CONCLUSIONS: This study concludes that physical fitness reduces intraocular pressure. Whether exercise conditioning has a role as a nonpharmacologic approach or as an addition to medical therapy must be left to future investigations.

Adult↗

PubMed1993

Myasthenia gravis: effect on antibody binding of conservative substitutions of amino acid residues forming the main immunogenic region of the nicotinic acetylcholine receptor.

In Myasthenia Gravis most anti-acetylcholine receptor (AChR) antibodies are against a highly conserved area of the AChR alpha-subunit called the Main Immunogenic Region (MIR). Amino acid residues critical for MIR formation have been located within the sequence alpha 67-76. In the present study, binding of anti-AChR monoclonal antibodies (mAbs) to synthetic peptide analogues of the sequence alpha 67-76 of human and Torpedo AChRs containing conservative single-residue substitutions identified the amino acid residues most important to the antigenicity of the MIR sequence, and offered clues to its tridimensional structure. Conservative substitutions of residues Asn68 and Asp71 greatly diminished mAb binding, identifying them as critical contact residues for anti-MIR mAbs. Substitutions at Asp70 and Tyr72 moderately affected binding. Cross-reactive mAbs originally raised against Electrophorus AChR bound single residue-substituted synthetic peptides in a manner consistent with the possibility that Electrophorus AChR may have a glutamic acid residue at position alpha 70 or alpha 71. Substitutions at residues Asp/Ala70 and Val/Ile70 between human and Torpedo alpha-subunits may be size-compensating, suggesting these amino acids in the native AChR may be in closer proximity than proposed in previous models of the MIR.

Amino Acid Sequence↗

PubMed1993

[Effects of praeruptorin-C on cytosolic free calcium in cultured rat heart cells].

The negative inotropic effect of Pra-C was supposed to be related to the blocking of extracellular calcium influx but direct evidence is not known. We, therefore, examined the effects of Pra-C on [Ca2+]i in isolated rat ventricular myocytes using the fluorescent Ca(2+)-indicator Fura-2/AM. It was found that Pra-C inhibited the elevation of [Ca2+]i induced by potassium-depolarization, high extracellular calcium and calcium agonist Bay K 8644 in a dose-dependent manner. At 1.0 mumol.L-1, it decreased the [Ca2+]i at the presence of 75 mmol.L-1 KCl, 10 mol.L-1 CaCl and 3 mumol.L-1 Bay K 8644 by 50, 31 and 42% respectively. No significant effect on ouabain evoked [Ca2+]i increase was found, showing that it does not affect sarcolemmal Na(+)-Ca2+ exchange. These results further indicate that Pra-C may decrease the [Ca2+]i of myocyte by blocking voltage-dependent calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1993

[Clinical analysis of 150 cases with periampullary carcinoma].

This article reported 150 cases of patients with periampullary carcinoma, among which cancer of 85 cases was in the head of pancreas, 26 in lower part of the common bile-duct, and 21 in ampulla of Vater and 18 in duodenal papilla. In 150 patients, pancreatoduodenectomy was performed in 53 cases but one had total pancreatectomy with a total resection rate of 36%. Resectability was high with cancer in ampulla and duodenal papilla, with a resection rate of 89.5% and 83.3%, respectively. The lowest resection rate, 14.1%, was in patients with cancer in head of the pancreas. Twenty cases had postoperative complications, the morbidity rate was 13.3%. Postoperative death occurred in 9 cases with a mortality rate of 6%. The resection group and non-resection group had 7.5 percent and 5.2 percent of the mortality respectively. Following-up showed that the 3 year and 5 year survival rates were 31.8% and 11.8% respectively. Fifty-four cases with resections had a mean survival period of 16.7 months. Ampullary carcinoma group had the longest survival period, 22.4 months, but non-resection group, all had bile-intestinal shunt, only 4.8 months.

Adult↗

PubMed1992

Computer controlled stereotaxic radiotherapy system.

A computer-controlled stereotaxic radiotherapy system based on a low-frequency magnetic field technology integrated with a single fixation point stereotaxic guide has been designed and instituted. The magnetic field, generated in space by a special field source located in the accelerator gantry, is digitized in real time by a field sensor that is six degree-of-freedom measurement device. As this sensor is an integral part of the patient stereotaxic halo, the patient position (x, y, z) and orientation (azimuth, elevation, roll) within the accelerator frame of reference are always known. Six parameters--three coordinates and three Euler space angles--are continuously transmitted to a computer where they are analyzed and compared with the stereotaxic parameters of the target point. Hence, the system facilitates rapid and accurate patient set-up for stereotaxic treatment as well as monitoring of patient during the subsequent irradiation session. The stereotaxic system has been developed to promote the integration of diagnostic and therapeutic procedures, with the specific aim of integrating CT and/or MR aided tumor localization and long term (4- to 7-week) fractionated radiotherapy of small intracranial and ocular lesions.

Electromagnetic Phenomena↗

PubMed1992

Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.

In myasthenia gravis (MG) an autoimmune response against muscle acetylcholine receptor (AChR) occurs. Embryonic muscle AChR contains a gamma subunit, substituted in adult muscle by a homologous epsilon subunit. Antibodies and CD4+ cells specific for embryonic AChR have been demonstrated in MG patients. We identified sequence segments of the human gamma subunit forming epitopes recognized by four embryonic AChR-specific CD4+ T cell lines, propagated from MG patients' blood by stimulation with synthetic peptides corresponding to the human gamma subunit sequence. Each line had an individual epitope repertoire, but two 20-residue sequence regions were recognized by three lines of different HLA haplotype. Most T epitope sequences were highly diverged between the gamma and the other AChR subunits, confirming the specificity of the T cells for embryonic AChR. These T cells may have been sensitized against AChR expressed by a tissue other than innervated skeletal muscle, possibly the thymus, which expresses an embryonic muscle AChR-like protein, containing a gamma subunit. Several sequence segments forming T epitopes are similar to regions of microbial and/or mammalian proteins unrelated to the AChR. These findings are consistent with the possibility that T cell cross-reactivity between unrelated proteins ("molecular mimicry"), proposed as a cause of autoimmune responses, is not a rare event.

Adult↗

PubMed1992

CD4+ T-epitope repertoire on the human acetylcholine receptor alpha subunit in severe myasthenia gravis: a study with synthetic peptides.

The alpha subunit of the nicotinic acetylcholine receptor (AChR) seems crucial in the pathogenesis of the autoimmune paralysis myasthenia gravis (MG) because it contains both the epitopes that dominate the antibody response against the AChR and those recognized by CD4+ AChR-specific T helper (Th) cells. To define the repertoire of anti-AChR Th cells, we investigated the response of unselected blood CD4+ cells or total lymphocytes, or both, from 22 MG patients to 20-residue overlapping synthetic peptides, screening the complete sequence of human-muscle AChR alpha subunit. Several epitopes were identified. Only the most severely affected patients recognized alpha subunit epitopes, and they were mainly young women. Detection of in vitro AChR-specific CD4+ response was facilitated by removal of the CD8+ cells because in two patients a clear response to several alpha subunit peptide sequences could be detected when CD(8+)-depleted cells were used, while their total peripheral blood mononuclear cell population did not respond to any alpha subunit peptide. Although each patient had a unique pattern of peptide recognition, four immunodominant regions recognized by long-term AChR-specific CD4+ T-cell lines, or flanking peptide sequences, were recognized most frequently (residues 48-67, 101-137, 293-337, and 308-437).

Amino Acid Sequence↗

PubMed1991

Structural determinants within residues 180-199 of the rodent alpha 5 nicotinic acetylcholine receptor subunit involved in alpha-bungarotoxin binding.

Synthetic peptides corresponding to sequence segments of the nicotinic acetylcholine receptor (nAChR) alpha subunits have been used to identify regions that contribute to formation of the binding sites for cholinergic ligands. We have previously defined alpha-bungarotoxin (alpha-BTX) binding sequences between residues 180 and 199 of a putative rat neuronal nAChR alpha subunit, designated alpha 5 [McLane, K. E., Wu, X., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 9816-9824], and between residues 181 and 200 of the chick neuronal alpha 7 and alpha 8 subunits [McLane, K. E., Wu, X., Schoepfer, R., Lindstrom, J., & Conti-Tronconi, B. M. (1991) J. Biol. Chem. (in press)]. These sequences are relatively divergent compared with the Torpedo and muscle nAChR alpha 1 alpha-BTX binding sites, which indicates a serious limitation of predicting functional domains of proteins based on homology in general. Given the highly divergent nature of the alpha 5 sequence, we were interested in determining the critical amino acid residues for alpha-BTX binding. In the present study, the effects of single amino acid substitutions of Gly or Ala for each residue of the rat alpha 5(180-199) sequence were tested, using a competition assay, in which peptides compete for 125I-alpha-BTX binding with native Torpedo nAChR.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1991

The I-Abm12 mutation, which confers resistance to experimental myasthenia gravis, drastically affects the epitope repertoire of murine CD4+ cells sensitized to nicotinic acetylcholine receptor.

Susceptibility to experimental autoimmune myasthenia gravis (EAMG), which is induced in mice by injection of purified Torpedo nicotinic acetylcholine receptor (TAChR), is influenced by the I-A locus products, which restrict presentation of AChR Th epitopes. The bm12 mutation of the I-Ab molecule in the C57BL/6 strain, which is highly susceptible to EAMG, yields the EAMG resistant mutant B6.C-H-2bm12 (bm12). We investigated here the consequences of the bm 12 mutation on the CD4+ response to the TAChR alpha subunit. Upon immunization with TAChR, CD4+ cells became sensitized to TAChR and anti-AChR antibodies were produced in both bm12 and C57BL/6 strains. Overlapping synthetic peptides, corresponding to the complete sequence of TAChR alpha subunit, were used to identify Th epitopes. CD4+ cells from C57BL/6 mice recognized peptides T alpha 150-169, T alpha 181-200, and T alpha 360-378. CD4+ cells from bm12 mice did not respond to any synthetic sequence. Upon injection of the three C57BL/6 Th epitope peptides, either individually or as a pool, CD4+ cells from C57BL/6 mice recognized each peptide and TAChR. Therefore they recognized epitopes similar or identical to those originated from TAChR processing. CD4+ cells from bm12 mice injected with the same peptides responded to T alpha 360-378 strongly, to a lesser extent to T alpha 181-200, never to peptide T alpha 150-169. Only CD4+ cells sensitized against the T epitope peptide T alpha 181-200 responded to TAChR. We tested if lack of response to T alpha 150-169, and the low response to T alpha 181-200, was due to inability of the I-Abm12 molecule to present the T epitope peptides. bm12 and C57BL/6 APC were used to present the T epitope peptides to specifically sensitized CD4+ cells from C57BL/6 mice. All T epitope peptides were presented by bm12 APC, although T alpha 150-169 was presented less efficiently than by C57BL/6 APC. Resistance to EAMG induced by the bm12 mutation may be due to the change in the epitope repertoire of AChR-specific Th cells, and lack of recognition of otherwise immunodominant Th epitopes. For at least one epitope this might be due to absence of potentially reactive, specific CD4+ clones.

Animals↗

PubMed1991

Identification of sequence segments forming the alpha-bungarotoxin binding sites on two nicotinic acetylcholine receptor alpha subunits from the avian brain.

The relationship between neuronal alpha-bungarotoxin binding proteins (alpha BGTBPs) and nicotinic acetylcholine receptor function in the brain of higher vertebrates has remained controversial for over a decade. Recently, the cDNAs for two homologous putative ligand binding subunits, designated alpha BGTBP alpha 1 and alpha BGTBP alpha 2, have been isolated on the basis of their homology to the N terminus of an alpha BGTBP purified from chick brain. In the present study, a panel of overlapping synthetic peptides corresponding to the complete chick brain alpha BGTBP alpha 1 subunit and residues 166-215 of the alpha BGTBP alpha 2 subunits were tested for their ability to bind 125I-alpha BGT. The sequence segments corresponding to alpha BGTBP alpha 1-(181-200) and alpha BGTBP alpha 2-(181-200) were found to consistently and specifically bind 125I-alpha BGT. The ability of these peptides to bind alpha BGT was significantly decreased by reduction and alkylation of the Cys residues at positions 190/191, whereas oxidation had little effect on alpha BGT binding activity. The relative affinities for alpha BGT of the peptide sequences alpha BGTBP alpha 1-(181-200) and alpha BGTBP alpha 2-(181-200) were compared with those of peptides corresponding to the sequence segments Torpedo alpha 1-(181-200) and chick muscle alpha 1-(179-198). In competition assays, the IC50 for alpha BGTBP alpha 1-(181-200) was 20-fold higher than that obtained for the other peptides (approximately 2 versus 40 microM). These results indicate that alpha BGTBP alpha 1 and alpha BGTBP alpha 2 are ligand binding subunits able to bind alpha BGT at sites homologous with nAChR alpha subunits and that these subunits may confer differential ligand binding properties on the two alpha BGTBP subtypes of which they are components.

Acetylcholine↗

PubMed1991

Structural determinants of alpha-bungarotoxin binding to the sequence segment 181-200 of the muscle nicotinic acetylcholine receptor alpha subunit: effects of cysteine/cystine modification and species-specific amino acid substitutions.

The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) alpha subunit forms a binding site for alpha-bungarotoxin (alpha-BTX) [e.g., see Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Spencer, S. R., Reinhardt-Maelicke, S., & Maelicke, A. (1990) Biochemistry 29, 6221-6230]. Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR alpha 1 subunits were tested for their ability to bind 125I-alpha-BTX, and differences in alpha-BTX affinity were determined by using solution (IC50S) and solid-phase (KdS) assays. Panels of overlapping peptides corresponding to the complete alpha 1 subunit of mouse and human were also tested for alpha-BTX binding, but other sequence segments forming the alpha-BTX site were not consistently detectable. The Torpedo alpha 1(181-200) and the homologous frog and chicken peptides bound alpha-BTX with higher affinity (KdS approximately 1-2 microM, IC50s approximately 1-2 microM) than the human and calf peptides (Kds approximately 3-5 microM, IC50s approximately 15 microM). The mouse peptide bound alpha-BTX weakly when attached to a solid support (Kd approximately 8 microM) but was effective in competing for 125I-alpha-BTX in solution (IC50 approximately 1 microM). The cobra nAChR alpha 1-subunit peptide did not detectably bind alpha-BTX in either assay. Amino acid substitutions were correlated with alpha-BTX binding activity peptides from different species. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased alpha-BTX binding, whereas oxidation of the peptides had little effect. Modifications of the cysteine/cystine residues of the cobra peptide failed to induce alpha-BTX binding activity. These results indicate that while the adjacent cysteines are likely to be involved in forming the toxin/alpha 1-subunit interface a vicinal disulfide bound was not required for alpha-BTX binding.

Amino Acid Sequence↗

PubMed1991

Amino acid residues forming the interface of a neuronal nicotinic acetylcholine receptor with kappa-bungarotoxin: a study using single residue substituted peptide analogs.

kappa-Bungarotoxin is a high affinity antagonist of neuronal nicotinic acetylcholine receptors of the alpha 3 subtype. Three sequence segments of the alpha 3 subunit that contribute to forming the binding site for kappa-bungarotoxin were previously located using synthetic peptides corresponding to the complete alpha 3 subunit, i.e., alpha 3(1-18), alpha 3(50-71) and alpha 3(180-201). Here we use single residue substituted peptide analogs of the alpha 3(50-71) sequence, in which amino acids are sequentially replaced by Gly, to determine which residues are important for kappa-bungarotoxin binding activity. Although no single substitution obliterated kappa-bungarotoxin binding, several amino acid substitutions lowered the affinity for kappa-bungarotoxin--i.e., two negatively charged residues (Glu51 and Asp62), and several aliphatic and aromatic residues (Leu54, Leu56, and Tyr63). These results indicate that the interface of the alpha 3 subunit with kappa-bungarotoxin involves primarily hydrophobic interactions, and a few negatively charged residues.

Amino Acid Sequence↗