安氟醚对大鼠皮层、海马、脑干腺苷酸环化酶及磷酸二酯酶活性的影响

目的观察安氟醚麻醉后大鼠不同脑区、不同时期腺苷酸环化酶(Adenylatecyclase ,AC)及磷酸二酯酶(Phosphodisterase ,PDE)活性的动态变化,并探讨cAMP在其麻醉中的可能作用。方法SD大鼠40只,随机分成5组,每组8只,吸入1 5 %的安氟醚,分别在未吸入安氟醚时(对照组)、翻正反射即将消失时(诱导期组)、翻正反射消失后2min(麻醉期组)、翻正反射恢复即刻(恢复期组)和翻正反射恢复后1h(清醒期组)断头取脑。放射性同位素法测定大脑皮层、海马和脑干的腺苷酸环化酶及磷酸二酯酶活性。结果在皮层,与对照组相比,AC活性在诱导期时开始升高,麻醉期时及恢复期时明显高于对照组( P <0 0 5 ) ,清醒期时恢复至对照组水平;PDE活性在诱导期时和麻醉期时均低于对照组( P <0 0 5 )。在海马,与对照组相比,AC活性只在麻醉期时升高明显(P <0 0 5 ) ;PDE活性在诱导期时和麻醉期时下降明显(P <0 0 5 ,P <0 0 1)。在脑干,与对照组比,AC活性在诱导期、麻醉期和恢复期均高于对照组(P <0 0 5 ) ;PDE活性只在麻醉期下降显著,(P <0 0 5 )。结论安氟醚升高大脑皮层、海马及脑干的腺苷酸环化酶活性,降低了磷酸二酯酶活性,从而增加了cAMP的含量,提示cAMP在安氟醚的全麻机制中可能发挥重要作用。     

Functional Profile of the Isolated Uremic Nephron: IMPAIRED WATER PERMEABILITY AND ADENYLATE CYCLASE RESPONSIVENESS OF THE CORTICAL COLLECTING TUBULE TO VASOPRESSIN

Resistance of the chronically diseased kidney to vasopressin has been proposed as a possible explanation for the urinary concentrating defect of uremia. The present studies examined the water permeability and adenylate cyclase responsiveness of isolated cortical collecting tubules (CCT) from remnant kidneys of uremic rabbits to vasopressin. In the absence of vasopressin the CCTs of both normal and uremic rabbits were impermeable to water. At the same osmotic gradient, addition of a supramaximal concentration of vasopressin to the peritubular bathing medium led to a significantly lower net water flux per unit length (and per unit luminal surface area) in uremic CCTs than in normal CCTs. Transepithelial osmotic water permeability coefficient, P(f), was 0.0232 +/-0.0043 cm/s in normal CCTs and 0.0059+/-0.001 cm/s in uremic CCTs (P < 0.001). The impaired vasopressin responsiveness of the uremic CCTs was observed whether normal or uremic serum was present in the bath.Basal adenylate cyclase activity per microgram protein was comparable in normal and uremic CCTs. Stimulation by NaF led to equivalent levels of activity in both, whereas vasopressin-stimulated activity was 50% lower in the uremic than in the normal CCTs (P < 0.025).The cyclic AMP analogue, 8-bromo cyclic AMP, produced an increase in the P(f) of normal CCTs closely comparable to that observed with vasopressin. In contrast, the P(f) of uremic CCTs was only minimally increased by this analogue and was not further stimulated by theophylline.These studies demonstrate an impaired responsiveness of the uremic CCT to vasopressin. This functional defect appears to be a result, at least in part, of a blunted responsiveness of adenylate cyclase to vasopressin. The data further suggest that an additional defect in the cellular response to vasopressin may exist, involving a step (or steps) subsequent to the formation of cyclic AMP.A unifying concept of the urinary concentrating defect of uremia is proposed which incorporates a number of hitherto unexplained observations on the concentrating and diluting functions of the diseased kidney.     

Sequence of Events Mediating the Effect of Cholera Toxin on Rat Thymocytes

We have found that in rat thymocytes binding of [(125)I]choleragen is followed by cellular accumulation of cyclic 3',5'-AMP which, in turn, is followed by stimulation of amino acid transport. Binding of cholera toxin was complete by 30 min and remained constant for the subsequent 150 min. After stimulation by choleragen, cellular cyclic 3',5'-AMP became maximal by 30 min, after which it declined steadily so that by 90 min of incubation, cellular cyclic nucleotide levels were only 20% of those seen at 30 min. Stimulation of amino acid transport, although detectable by 15 min, did not become maximal until 120 min (by which time cellular cyclic 3',5'-AMP had decreased by more than 80%). We have also used this system to delineate the step at which various pharmacologic agents and hormones act to alter the sequence of events mediating the response of rat thymocytes to cholera toxin. The ability of cycloheximide to abolish choleragen-stimulated amino acid influx without reducing [(125)I]choleragen binding or cellular cyclic 3',5'-AMP suggests that cyclic nucleotide stimulation of amino acid transport includes a step involving protein synthesis.     

Effect of Cholera Toxin on Intestinal Elimination of Ciprofloxacin in Rabbits

The transepithelial intestinal elimination of ciprofloxacin (CPX) was studied in cholera toxin (CT)-challenged and control intestinal loops in the rabbit. CPX concentrations were similar in CT-challenged and control jejunal and ileal loops, while cecal elimination was negligible. The quantities of eliminated CPX per square centimeter of bowel wall were significantly higher in the small intestine CT-challenged loops. The mechanism of elimination of CPX in the small intestine is therefore mainly passive diffusion.     

Characterization of the Human Platelet α-Adrenergic Receptor: CORRELATION OF [3H] DIHYDROERGOCRYPTINE BINDING WITH AGGREGATION AND ADENYLATE CYCLASE INHIBITION

Human platelets aggregate and undergo a release reaction when incubated with catecholamines. Indirect evidence indicates that these events are mediated through alpha-adrenergic receptors. We used [(3)H]dihydroergocryptine, an alpha-adrenergic antagonist, to identify binding sites on platelets that have the characteristics of alpha-adrenergic receptors. Catecholamines compete for the binding sites in a stereo-specific manner with the potency series of (-) epinephrine > (-) norepinephrine > (+/-) phenylephrine > (-) isoproterenol. The dissociation constant (K(d)) of (-) epinephrine is 0.34 muM. Binding is saturable using a platelet particulate fraction but not with intact platelets. There are 0.130 pmol binding sites per milligram protein in fresh platelet membranes. This number represents approximately 100 binding sites per platelet. The K(d) for [(3)H]-dihydroergocryptine was 0.003-0.01 muM. The alpha-adrenergic antagonist phentolamine (K(d) = 0.0069 muM) was much more potent than the beta-adrenergic antagonist (+/-) propranolol (K(d) = 27 muM) in competing for the binding sites. The binding data were correlated with catecholamine-induced platelet aggregation and inhibition of basal and prostaglandin E(1)-stimulated adenylate cyclase. (-) Epinephrine was more potent than (-) norepinephrine in producing aggregation whereas (-) isoproterenol was ineffective. The threshold dose for inducing aggregation by (-) epinephrine was 0.46 muM. Phentolamine and dihydroergocyrptine blocked this response, whereas (+/-) propranolol had no effect. (-) Epinephrine and (-) norepinephrine inhibited basal and prostaglandin E(1)-stimulated adenylate cyclase in a dose-related manner. The concentration of (-) epinephrine inhibiting adenylate cyclase 50% was 0.7 muM. This inhibition was also blocked by phentolamine and dihydroergocryptine but not by (+/-) propranolol. The specificity of binding and the close correlation with alpha-adrenergic receptor-mediated biochemical and physiological responses suggest that the [(3)H]dihydroergocryptine binding site represents, or is closely related to, the human platelet alpha-adrenergic receptor. The ability to assay this receptor directly and to correlate these data with independently measured sequelae of receptor activation should facilitate increased understanding of the physiology and pathophysiology of the human platelet alpha-adrenergic receptor.     

Mutants in the ADP-ribosyltransferase Cleft of Cholera Toxin Lack Diarrheagenicity but Retain Adjuvanticity

Cholera toxin (CT), the most commonly used mucosal adjuvant in experimental animals, is unsuitable for humans because of potent diarrhea-inducing properties. We have constructed two CT-A subunit mutants, e.g., serine→ phenylalanine at position 61 (S61F), and glutamic acid→ lysine at 112 (E112K) by site-directed mutagenesis. Neither mutant CT (mCT), in contrast to native CT (nCT), induced adenosine diphosphate-ribosylation, cyclic adenosine monophosphate formation, or fluid accumulation in ligated mouse ileal loops. Both mCTs retained adjuvant properties, since mice given ovalbumin (OVA) subcutaneously with mCTs or nCT, but not OVA alone developed high-titered serum anti-OVA immunoglobulin G (IgG) antibodies (Abs) which were largely of IgG1 and IgG2b subclasses. Although nCT induced brisk IgE Ab responses, both mCTs elicited lower anti-OVA IgE Abs. OVA-specific CD4⁺ T cells were induced by nCT and by mCTs, and quantitative analysis of secreted cytokines and mRNA revealed a T helper cell 2 (Th2)-type response. These results now show that the toxic properties of CT can be separated from adjuvanticity, and the mCTs induce Ab responses via a Th2 cell pathway.The major enterotoxins produced by Vibrio cholerae and Escherichia coli, termed cholera toxin (CT)¹ and heatlabile toxin (LT), respectively, are multisubunit macromolecules composed of two structurally, functionally, and immunologically separate A and B subunits (1–3). The B subunit of each toxin consists of five identical 11.6-kD peptides, but differ from each other in that the B subunit of CT (CT-B) only binds to GM1 ganglioside (4), whereas the B subunit of LT (LT-B) binds GM1 as well as asialo GM1 and GM2 (5). After the B subunit binds to epithelial cell GM1 or GM2 receptors, the A subunit reaches the cytosol, and after activation, binds to nicotinamide adenosine diphosphate and catalyzes ADP ribosylation of Gs-α (6). This GTP-binding protein activates adenyl cyclase with subsequent elevation of cAMP, which in epithelial cells results in secretion of water and chloride ions into the small intestine (7).Both CT and LT are immunogenic and mucosal exposure results in secretory IgA (S-IgA) and serum Abs, which are almost entirely restricted to CT-B or LT-B (8, 9). Further, both toxins are also strong mucosal adjuvants for coadministered, unrelated protein Ags when given by oral, intranasal, or parenteral routes (8–10). We have shown that induction of maximal mucosal S-IgA and serum IgG Ab responses correlated directly with Ag-specific CD4⁺ Th cells secreting IL-4 and IL-5 in mice orally immunized with protein Ag and CT as adjuvant (10). Further, detailed analysis showed that CT elicits adjuvant responses by inducing Ag-specific CD4⁺ Th2-type cells which produce high levels of IL-4 and IL-5, responsible for supporting subsequent development of systemic IgG1 and IgG2b subclass, IgE and S-IgA Ab responses (11). On the other hand, oral immunization with LT promotes IgM, IgG1, IgG2a, IgG2b, and S-IgA Ab responses, which are supported by a mixed CD4⁺ Th1- and Th2-type response associated with IFN-γ, IL-4, IL-5, IL-6, and IL-10 production (12). Furthermore, when IL-4 levels produced by CD4⁺ T cells were compared when CT or LT were used as adjuvants, Ag-specific IL-4 production was lower when LT was used (11, 12).Earlier studies have attempted to dissociate toxicity from adjuvanticity of CT and LT; however, it was shown that a mutant LT toxin, E112K, which had single amino acid substitution in the ADP-ribosyltransferase active center, was nontoxic and also lacked adjuvanticity (13). Recently, two groups have reported that single amino acid substitution mutants of LT, R7K, and R192G, which are outside of the ADP-ribosyltransferase cleft, were nontoxic, but retained adjuvant properties (14, 15). However, one of these LT mutants retained some ADP-ribosyltransferase activity and could potentially cause diarrhea in humans.To develop an ideal nontoxic mucosal adjuvant, we constructed two CT mutants, S61F and E112K, by site-directed mutagenesis, which have single amino acid substitutions in the ADP-ribosyltransferase active center (16). Neither mutant showed toxic activity, and in the present study these mutants were used to assess adjuvant properties as well as signaling pathways involved in adjuvanticity.     

Mode of Action of Polymyxin B: Physiological Studies with a Bacillus subtilis-Resistant Mutant

Polymyxin B resistance in Bacillus subtilis can be suppressed by the synergistic action of lysozyme or of an analogous cell wall lytic activity released by B. subtilis spores during germination.Such a synergistic effect is probably due to partial cell-wall digestion by lysozyme that allows polymyxin to reach its site of action and is therefore distinct from the analogous synergistic effect described by other authors in Escherichia coli. In the latter case polymyxin B probably damaged the outer membrane, allowing lysozyme to reach and digest the cell wall.     

Preliminary Studies of the Mode of Action of Arildone, a Novel Antiviral Agent

Arildone (also known as Win 38020), a novel aryl diketone, inhibited replication of herpes simplex virus type 2 in tissue culture by interfering with an event that occurs prior to 6 h postinfection. The inhibition could be partially reversed by washing. Although the exact mechanism of action is unknown, neither viral deoxyribonucleic acid nor viral proteins were synthesized in the presence of arildone.     

The Regulation of Skeletal Muscle Alanine and Glutamine Formation and Release in Experimental Chronic Uremia in the Rat: SUBSENSITIVITY OF ADENYLATE CYCLASE AND AMINO ACID RELEASE TO EPINEPHRINE AND SEROTONIN

The mechanism of the increased alanine and glutamine formation and release from skeletal muscle in experimental uremia was investigated using epitrochlearis preparations from control and chronically uremic rats. In uremic muscle, insensitivity to epinephrine or serotonin suppression of alanine and glutamine release was observed. With control muscles, 1 nm or greater, epinephrine inhibited alanine and glutamine release, whereas with uremic muscles, epinephrine concentrations <1 muM did not alter amino acid release. Decreased alanine and glutamine release with 1 nM serotonin was observed in control muscles, but no inhibition was observed with concentrations <1 muM in uremic muscle. Muscle amino acid levels were the same in control and uremic muscles in the presence or absence of epinephrine or serotonin. The reutilization of released alanine by protein synthesis or oxidation to CO(2) was not differentially affected by epinephrine in uremic muscles as compared with control muscle. Dibutyryl-cAMP inhibited amino acid release equally in uremic and control muscles. Epinephrine or serotonin increased cAMP levels two- to four-fold or more in control than in uremic muscle. Basal- and fluoride-stimulated adenylate cyclase activities were equal in uremic and control muscle homogenates and in membrane fractions, but 10 muM epinephrine-stimulated adenylate cyclase was reduced 30-60% with uremia. At any concentration of epinephrine (0.001-100 muM), the stimulation of membrane adenylate cyclase activity was one- to twofold greater with control membranes than with uremic muscle membranes. With either control or uremic muscle, peak adenylate cyclase activity was observed at 1 muM epinephrine.These data indicate that skeletal muscle in chronic uremia acquires an insensitivity to the metabolic action of epinephrine or serotonin. This insensitivity may be attributable in part to the diminished increments in muscle cAMP levels produced by adrenergic and serotonergic agonists. The decreased cAMP levels may derive in turn from a decreased activity or subsensitization of the agonist-stimulated adenylate cyclase in uremic muscle.     

Studies on the Mechanism of Action of Nalidixic Acid

With three independent techniques (absorption spectrophotometry, measurement of the deoxyribonucleic acid [DNA] melting temperature, and equilibrium dialysis), no evidence has been found for the binding of nalidixic acid to purified DNA. Also, no evidence has been found to support the hypothesis that nalidixic acid is permanently modified to a new, active compound by the bacterial cell. By using an in vitro DNA replication system developed by Bonhoeffer and colleagues, soluble extracts from nalidixic acid-sensitive cells have been shown to confer nalidixic acid sensitivity on the DNA synthesis of lysates from nalidixic acid-resistant cells. The activity in the extracts is only present in sensitive cells and is nondialyzable and heat sensitive. Finally, two known nalidixic acid-resistant mutants of Escherichia coli, mapping at nal A and nal B, respectively, have been tested to determine whether either of them is a transport mutant. It has been shown that nal B(r) is a transport mutant whereas nal A(r) is not.     

A Study of Intercellular Spaces in the Rabbit Jejunum during Acute Volume Expansion and after Treatment with Cholera Toxin

The effects of acute volume expansion and of intraluminal administration of cholera toxin have been examined in rabbit jejunum.     

Central Sensitization in the Trigeminal Nucleus Caudalis Produced by a Conjugate of Substance P and the A Subunit of Cholera Toxin

Individuals with chronic craniofacial pain experience symptoms that are consistent with central sensitization. In fact, central sensitization may constitute the major disease process in these conditions, particularly if the original injury has healed or the condition is idiopathic. To understand central sensitization we have developed a conjugate of substance P and cholera toxin (SP-CTA). SP-CTA is selectively taken up by cells that express neurokinin receptors. Twenty-four hours following intracisternal administration of SP-CTA, wild-type rats and mice demonstrated signs of persistent background nociception, but when tested for facial cold sensitivity, they did not differ from controls. However, treating the SP-CTA–injected animals with naloxone exposed cold hypersensitivity in the face. Mu-opioid receptor knockout mice treated with SP-CTA demonstrated hypersensitivity without naloxone treatment. These findings suggest that central sensitization leads to activation of an endogenous opioid system. The data also demonstrate that the intracisternal administration of SP-CTA in rodents is a useful model for studying central sensitization as a disease process without having to induce a peripheral injury.PerspectiveCentral sensitization is a concern in many craniofacial pain conditions. In this project, we utilize a conjugate of substance P and the catalytic subunit of cholera toxin to induce central sensitization in the nucleus caudalis of rodents. The data indicate that the injected animals become hypersensitive in the face.     

Effects of Cholera Enterotoxin on Adenosine 3′,5′-Monophosphate and Neutrophil Function. COMPARISON WITH OTHER COMPOUNDS WHICH STIMULATE LEUKOCYTE ADENYL CYCLASE

Cholera enterotoxin caused a delayed accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in human leukocytes, associated with an increase in leukocyte adenyl cyclase activity. The action of cholera enterotoxin contrasted with that of other agents which stimulate adenyl cyclase: (a) the effects of the toxin were delayed in onset, while prostaglandin-E(1) (PGE(1)) and isoproterenol acted rapidly; (b) removal of the soluble toxin from the extracellular medium did not abolish its effects on cyclic AMP and inhibition of antigenic histamine release, while removal of PGE(1) did prevent its effects; (c) PGE(1), but not cholera enterotoxin, stimulated adenyl cyclase activity when added directly to broken cell preparations. Binding of the toxin to leukocytes was rapid and irreversible, and was followed by a gradual increase in cyclic AMP which was not prevented by cycloheximide.Cholera enterotoxin caused accumulation of cyclic AMP in purified human neutrophils as well as mono-nuclear cells, but did not prevent the extrusion of lysosomal hydrolases from phagocytic cells. The toxin only slightly inhibited the ability of human neutrophils to kill Candida albicans. Thus these results with the toxin cast doubt on previous proposals that cyclic AMP regulates these two functions of neutrophils. The unique action of cholera enterotoxin on cyclic AMP production provides a potentially useful pharmacologic tool, in addition to methylxanthines and dibutyryl cyclic AMP, for testing hypotheses relating cyclic AMP to altered function of leukocytes and, perhaps, of other mammalian cells.     

Studies on the Action of Nalidixic Acid in the Yeast Saccharomyces cerevisiae

The effect of the antibiotic nalidixic acid on macromolecular metabolism in the yeast Saccharomyces cerevisiae has been studied. It was found that, upon the addition of nalidixic acid to a logarithmically growing culture, there is a transient inhibition of total cell ribonucleic acid, deoxyribonucleic acid, and protein synthesis, after which the cells show an almost complete recovery. In addition, there is no preferential inhibition of yeast mitochondrial deoxyribonucleic acid synthesis.     

Mode of Action of Quindoxin and Substituted Quinoxaline-di-N-Oxides on Escherichia coli

The effect of quindoxin on the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid, and protein in Escherichia coli KL 399 was examined under aerobic and anaerobic conditions. In the absence of oxygen the synthesis of DNA was completely inhibited by 10 ppm of quindoxin, whereas the syntheses of ribonucleic acid and protein were not affected. Quinoxalin-di-N-oxides (QdNO) induce degradation of DNA in both proliferating and non-proliferating cells. polA, recA, recB, recC, exrA, and uvrA mutants were more susceptible than the corresponding repair-proficient strains. All strains were more resistant in the presence of oxygen. Quindoxin was reduced to quinoxalin-N-oxide by intact E. coli cells or by a cell-free E. coli extract. Electron spin resonance measurements demonstrated the generation of free radicals during the reduction of quindoxin. Oxygen or deficiency of energy sources impaired the antibiotic activity and the reduction of QdNO. The QdNO reductase activity was demonstrated to be lower in QdNO-resistant mutants than in the susceptible parent strain. Based on these results it is concluded that an intermediate of reduction, probably a free radical, is responsible for the lethal effect of quindoxin. With three independent techniques no evidence has been found for binding of quindoxin to DNA.     

Mode of Action of Lividomycin on Protein Synthesis in Escherichia coli

Lividomycin specifically inhibited bacterial protein synthesis and had codon misreading activity. Lividomycin, moreover, stimulated the binding of aminoacyl-transfer ribonucleic acid to ribosomes, but did not show any significant effects on the formation of aminoacyl-transfer ribonucleic acid and the puromycin reaction.     

霍乱毒素B亚单位-神经生长因子耦联制剂滴鼻对拟痴呆小鼠空间学习记忆的影响

目的观察霍乱毒素B亚单位(cholera toxin B subunit, CB)与神经生长因子(NGF)耦联制剂滴鼻治疗对拟痴呆小鼠学习记忆能力及胆碱能神经系统的影响。方法用改进的过碘酸钠法使CB-NGF耦联,滴鼻治疗脑室内注射β样淀粉蛋白(Aβ_25-35)的拟AD小鼠模型;CB-NGF 7-5 μg/d、15 μg/d滴鼻治疗7 d,Morris水迷宫检测其空间学习记忆能力;免疫组织化学染色胆碱乙酰化酶(ChAT)。结果未经治疗的模型鼠寻台潜伏期明显延长(P<0-01);在安全岛所在象限的停留时间明显缩短,斜角带区ChAT阳性细胞数量显著减少(P<0-001)。NGF及CB-NGF滴鼻治疗组寻台潜伏期有所缩短,在安全岛象限内的停留时间比模型组明显延长(P<0-01);基底前脑斜角带区ChAT染色明显增多(P<0-01)。结论CB-NGF滴鼻治疗可改善痴呆小鼠的空间认知能力,与其保护胆碱能神经有关。     

Antimicrobial Activity of Amine Oxides: Mode of Action and Structure-Activity Correlation

The effect of N-alkyl derivatives of saturated heterocyclic amine oxides on the growth and metabolism of microorganisms has been studied. 4-Dodecylmorpholine-N-oxide inhibited the differentiation and growth of Bacillus cereus, of different species of filamentous fungi, and of the yeast Saccharomyces cerevisiae. For vegetative cells, the effect of 4-dodecylmorpholine-N-oxide was lethal. Cells of S. cerevisiae, after interaction with 4-dodecylmorpholine-N-oxide, released intracellular K(+) and were unable to oxidize or ferment glucose. The functions of isolated yeast mitochondria were also impaired. 4-Dodecylmorpholine-N-oxide at growth-inhibiting concentrations induced rapid lysis of osmotically stabilized yeast protoplasts, with the rate of lysis a function of temperature and of amine oxide concentration. A study of the relationships between structure, antimicrobial activity, and cytolytic activity was made with a group of structurally different amine oxides involving a series of homologous 4-alkylmorpholine-N-oxides, 1-alkylpiperidine-N-oxides, 1-dodecylpyrrolidine-N-oxide, 1-dodecylperhydroasepine-N-oxide, and N,N-dimethyldodecylamine oxide. Disorganization of the membrane structure after interaction of cells with the tested amine oxides was primarily responsible for the antimicrobial activity of the amine oxides. This activity was found to be dependent on the chain length of the hydrophobic alkyl group and was only moderately influenced by other substituents of the polarized N-oxide group.     

Genetic and Physiological Studies on the Site of Action of Distamycin A

Two new genetic loci of Bacillus subtilis are identified by mutations that confer resistance to distamycin A and to other antibacterial agents. The chromosomal region where they map probably contains a cluster of genes whose products are related to membrane structure and function. Some of the biological effects of distamycin A are still in evidence in the resistant mutants indicating that the drug possibly acts at multiple sites. Most biological effects of the drug (including the phenotypic correction of a morphopoietic mutation) are likely to be due to the interaction of distamycin A with membrane (or surface) structures.