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Biomedical subjects

S Batra

Publications and source records attributed to S Batra.

At least 145 records · Page 8Linked to original sources

Antioxidant enzymes in Acanthocheilonema viteae and effect of antifilarial agents.

Adult worms of Acanthocheilonema viteae were found to be susceptible to the reactive oxygen intermediates (ROI) generated by the xanthine-xanthine oxidase (X-XO) system. The damage caused by this system was completely abolished by superoxide dismutase (SOD) and catalase but not by mannitol. The results, therefore, suggest that superoxide anions (O2-) and hydrogen peroxide (H2O2) alone or in combination might be toxic to the filariid. A. viteae exhibited the presence of an active enzyme system to protect itself against the oxidants. SOD and catalase were present in high levels of activities and appeared to constitute the major defence system. The role of glutathione peroxidase (GPx), on the other hand, seemed less important due to the weak activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH). A. viteae also released SOD, catalase and GPx in the ambient medium, which appear useful in protecting the filariid against ROI generated by the host in the immediate surroundings of the parasite. Antifilarial agents, diethylcarbamazine (DEC) and 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (82/437) appreciably inhibited catalase and GPx of A. viteae. Inhibition of these enzymes appears to render the parasite prone to H2O2 toxicity leading to death. No adverse effect on antioxidant enzymes of liver, lungs and subcutaneous tissue of Mastomys natalensis recorded as a result of exposure to 82/437 suggests a non-toxic nature to the compound.

Animals↗

Characterization of muscarinic cholinergic receptors in membrane preparations from rat prostatic adenocarcinoma.

The binding characteristics of 3H-quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions from R-3327 Dunning tumors (H and AT-1 sublines); ventral, dorsolateral prostate; and urinary bladder of the rat were studied. QNB binding to all preparations, except from AT-1 tumors, was specific, saturable, and of high affinity. The AT-1 tumors completely lacked specific QNB binding. The muscarinic receptor density in H tumors was twofold and twentyfold higher than that in the ventral prostate and dorsolateral prostate respectively. The receptor density in the urinary bladder was approximately twofold higher than that in H tumors. The Kd values in H tumors and ventral prostate were very similar and significantly higher than that in dorsolateral prostate or the urinary bladder. QNB binding in H tumors was strongly inhibited by classical muscarinic receptor antagonists atropine and scopolamine, but poorly by the agonists carbacholine and pilocarpine. In contrast to scopolamine or atropine, inhibition by pirenzepine and AF-DX116 was relatively low. These data indicate that the muscarinic receptor in Dunning H tumors is of M3 type.

Animals↗

Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and calcium channel blockers in cell membranes.

The interaction of tamoxifen and clomifene with membrane binding sites for the cholinergic ligand quinuclidinyl benzilate (QNB) and the dihydropyridine calcium antagonist nitrendipine was studied. Both tamoxifen and clomifene competed with [3H]-QNB and [3H]-nitrendipine for their binding to the receptor in the membrane fractions from the urinary bladder and myometrium. The extent of inhibition as judged by the Ki values for both antiestrogens was similar at both receptor sites. The data suggest that the antiproliferative effects of tamoxifen may involve not only the intracellular estrogen-receptor system but also receptors for neurotransmitters and membrane calcium channels.

Animals↗

Reactive oxygen intermediates metabolizing enzymes in Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

Adult worms of Ancylostoma ceylanicum and Nippostronglyus brasiliensis were found to possess an active system for the detoxification of reactive oxygen intermediates. Xanthine oxidase, which is known to produce superoxide anion, was detected in both the nematode parasites in significant activities. Superoxide anion, thus produced, may quickly be eliminated by superoxide dismutase. Both parasites also exhibited the presence of catalase, peroxidase, and glutathione peroxidase for efficient removal of hydrogen peroxide. Glutathione reductase and glucose-6-phosphate dehydrogenase were, however, detected in low levels of activities. Endowment of A. ceylanicum and N. brasiliensis with these antioxidant enzymes, therefore, enables them to evade the host's effector mechanism for their survival. Superoxide dismutase of both these nematodes showed marked inhibition by KCN and, hence, the enzyme appears to be of copper-zinc type.

Ancylostoma↗

Influence of chronic oestrogen treatment on the density of muscarinic cholinergic receptors and calcium channels in the rabbit uterus.

Ovariectomized rabbits were treated for 1 or 8 weeks with oestrogen and the effects on uterine weight, muscarinic receptor density and nitrendipine-binding sites on myometrial membranes were studied. The wet weight of the uterus after 1 week of oestrogen treatment increased more than tenfold and increased further by approximately 50% after 8 weeks of oestrogen treatment. The muscarinic receptor density increased significantly after 1 week of oestrogen treatment. Although there was no further increase in receptor density with continuing oestrogen treatment up to 8 weeks, the muscarinic receptor affinity increased significantly. The density of nitrendipine-binding sites increased sixfold after 1 week of oestrogen treatment and did not change thereafter. Oestrogen treatment had no influence on the affinity of nitrendipine-binding sites. The increase by oestrogen in muscarinic receptor density and in nitrendipine-binding sites as shown by the present data is consistent with the generally reported increase in agonist-induced contractile response of the myometrium following oestrogen treatment.

Animals↗

Tissue specific effects of progesterone on progesterone and estrogen receptors in the female urogenital tract.

The effect of progesterone administration on progesterone and estrogen receptors in the uterus, vagina and urethra of rabbits was studied. After 24 h of progesterone treatment the concentration of cytosolic progesterone receptors decreased to about 25% of the control value in the uterus, whereas no significant change in receptor concentration was observed in the vagina or the urethra. The concentration of the nuclear progesterone receptor did not change in any of the three tissues studied. The apparent dissociation constant (Kd) of nuclear progesterone receptor increased after progesterone treatment in all three tissues. Although the Kd of the cytosolic progesterone receptor also increased in all tissues, the difference was significant for only the vagina and urethra. The concentration of cytosolic estrogen receptors in the uterus decreased significantly (P less than 0.001) after progesterone treatment whereas the Kd value increased slightly (P less than 0.05). In vagina or the urethra, there was no change in either estrogen receptor concentration or Kd values after progesterone treatment. These data clearly showed that the reduction by progesterone of progesterone and estrogen receptor concentrations occurs only in the uterus and not in the vagina or the urethra.

Animals↗

Oestrogen-induced changes in muscarinic receptor density and contractile responses in the female rabbit urinary bladder.

Mature ovariectomized rabbits were treated for 1, 4 or 8 weeks with oestrogen, and the effects on contractile responses and on muscarinic receptor density in the isolated urinary bladder were studied. Oestrogen treatment caused a significant increase in the weight of the bladders. The responses to K+ (124 mM) were depressed, but not the maximum responses to carbachol. The frequency-response curve to electrical stimulation was shifted to the right after 4 and 8 weeks of treatment, but the maximum response was not reduced. There was also a (non-significant) shift to the right of the carbachol concentration-response curve. Pre-treatment with scopolamine revealed a significant reduction of the non-cholinergic response to electrical stimulation after oestrogen treatment compared to controls. Binding of [3H]quinuclidinyl benzilate (QNB) was saturable and of high affinity. There were no changes in apparent dissociation constant after oestrogen treatment. However, the muscarinic receptor density decreased already after 1 week of treatment and was only 10% of the control after 4 weeks. It is concluded that oestrogen treatment causes a down-regulation of muscarinic receptors in the rabbit urinary bladder, but the consequences for contractile activation through muscarinic receptors seem to be small.

Animals↗

Xanthine oxidase, superoxide dismutase, catalase and lipid peroxidation in Mastomys natalensis: effect of Dipetalonema viteae infection.

Status of xanthine oxidase, superoxide dismutase, catalase and lipid peroxidation, the enzymes metabolizing reactive oxygen intermediates in liver, lungs and spleen of M. natalensis during D. viteae infection was investigated. Xanthine oxidase and lipid peroxidation exhibited stimulation, while superoxide dismutase and catalase showed depression in liver and spleen of the infected animals. The filarial infection therefore appears to create O2 toxicity in these tissues. Lungs, on the other hand was found safe as it possessed elevated xanthine oxidase, superoxide dismutase and catalase. Lipid peroxidation in lungs operated below the control level. The impact of these changes in the establishment and development of the infection has been discussed.

Analysis of Variance↗

Effect of calcium and calmodulin antagonists on contractile responses of the human uterine artery.

1. The dependence on extracellular calcium of contractile responses of intramyometrial arteries (0.5-2 mm diameter), as well as the effects of various types of calcium antagonists on these responses, were studied. Contractions were induced by K-depolarization (K) and noradrenaline (NA). 2. Whereas the K response was completely abolished in a calcium-free medium containing 2 mM LaCl3, the NA response was substantially maintained. 3. Nimodipine strongly inhibited the K response but had a relatively weak effect on the NA response; the IC50 values for the K and NA responses being 2 nM and 6 microM, respectively. Corresponding values for verapamil were about 0.7 and 10 microM. 4. Calmodulin antagonists, particularly trifluoperazine and flunarizine, caused a greater inhibition of the NA than of the K response. 5. These results indicate that besides the extracellular calcium which appears to be the major source of activator calcium, there is an intracellular pool of calcium which can be utilized to activate, albeit to a limited extent, drug-induced contractile responses.

Calcium↗

Extracellular and intracellular calcium sources mediating contractile responses of smooth muscle in bovine ovarian follicle and ovarian artery.

The relative importance of extracellular and intracellular calcium sources mediating smooth muscle contraction in ovarian follicle and ovarian artery was assessed in experiments on the influence of nifedipine, D-600, amrinone, diethylstilbestrol (DES), lanthanum and/or calcium removal on contractions induced by K+ depolarization, by noradrenaline, histamine and acetylcholine. The K+-induced response was biphasic in the ovarian artery but not in the ovarian follicle. The K+-induced contraction in both preparations was greatly inhibited by nifedipine (1 microM), D-600 (10 microM) and lanthanum (2 mM). Although both phases of the responses in the ovarian artery appeared to be completely dependent on extracellular calcium, phase I was significantly more sensitive to nifedipine than phase II. Incubation in calcium-free medium for 15 min almost abolished the K+-induced contraction. Noradrenaline- and histamine-induced contractions of ovarian follicle were essentially unaffected by nifedipine (1 microM) and D-600 (10 microM) whereas the noradrenaline-induced contraction in ovarian artery was inhibited significantly by D-600 (1 and 10 microM) but not nifedipine (1 microM). In calcium-free medium containing EGTA (1 mM) the responses of ovarian follicle to noradrenaline and histamine were reduced by 26 and 22% respectively. When preparations were stimulated with noradrenaline more than one in calcium-free medium, the contraction decreased progressively compared to time-matched controls. The response was 34% of the control after 50 min in calcium-free medium containing EGTA. In the ovarian artery the response obtained (6% of control) was significantly smaller (P less than 0.05) than that in the follicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of muscarinic acetylcholine binding in the urinary bladder and submandibular gland of the rabbit.

In order to explore the possibility of heterogeneity in peripheral muscarine receptors, receptors were characterized in membrane fractions isolated from rabbit urinary bladder and submandibular gland. With [3H]QNB as radioligand, specific binding with very high affinity was found in both preparations. Although the BmaxS for binding in the two preparations were very similar, the mean KD value in the submandibular gland was significantly higher (P less than 0.005) than that in the bladder. Among the anticholinergic drugs, oxybutynin had a significantly lower value for the inhibition constant (Ki) in the submandibular gland whereas Ki for both secoverine and pirenzepine was significantly higher in this tissue than in urinary bladder. The Ki for carbacholine was about 7-fold higher in submandibular gland than in the bladder. Although quinidine and verapamil showed relatively weak binding to the muscarine receptor site, their Ki in the submandibular gland was significantly higher than that in the bladder. The results indicate that although there is a considerable similarity between muscarinic receptors in urinary bladder and submandibular gland, the differences in Ki values for different compounds in the two tissues support the argument favouring heterogeneity of muscarinic acetylcholine receptors in peripheral effector organs.

Animals↗

Identification and characterization of muscarinic cholinergic receptors in the human urinary bladder and parotid gland.

The binding characteristics of [3H]quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions of the human urinary bladder and parotid gland were studied. QNB binding to both preparations was of high affinity and low capacity. Mean values for the apparent dissociation constants (Kd) for binding to membrane preparations from the urinary bladder and parotid glands were 22 and 34 pM and the Bmax values 234 and 456 fmol/mg protein, respectively. Significance of difference between Kd and Bmax values from the two tissues was at the level of P less than 0.005 and P less than 0.05, respectively. QNB binding was inhibited by muscarinic receptor antagonists with varying degree of effectiveness. The mean values for the inhibition constant (Ki) were significantly lower for oxybutynin, amitriptyline, and pirenzepine but higher for secoverine in preparations of the urinary bladder than of the parotid gland. The mean Ki values for quinidine and verapamil were lower in the urinary bladder than that in the parotid gland. Carbachol exhibited a marked selectivity for the urinary bladder (about 30-fold) compared with the parotid gland. The present data obtained in two human tissues that are highly cholinergic in their innervation give support to the argument for heterogeneity of the muscarinic cholinergic receptors.

Cell Membrane↗

Progesterone receptors in vaginal tissue of post-menopausal women.

Progesterone receptors were measured in both cytosolic and nuclear fractions in vaginal tissue samples obtained from a total of 17 post-menopausal women. Ten of the women were given oestriol (E3) intravaginally 6-24 h before surgery, while the remaining 7 received no treatment. Cytosolic receptors were not detected in any of the 7 tissue samples from the untreated women, but nuclear receptors were present in two cases. In the 10 women treated with E3, it was possible to measure cytosolic receptors in 5 tissue samples and nuclear receptors in 7 samples. The mean receptor concentrations in the cytosolic and nuclear fractions were similar (45-65 fmol/mg protein) and the apparent dissociation constant of the receptors in all the samples was 1-2 nmol/1. These data would seem to indicate that oestrogen treatment results in the synthesis of new receptors, although not in all tissues, which compounds the scepticism regarding the validity of the classical two-step model for steroid hormone action.

Administration, Intravaginal↗

Effects of calcium, calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man.

In isolated bladder smooth muscle from both rabbit and man, carbachol-induced contractions were reduced by the calcium channel blocker nifedipine, whereas the calcium channel promotor Bay K 8644 had no effect. In nominally calcium-free medium containing 10(-4) M EGTA, carbachol-induced contractions were reduced by 69% (rabbit) and 87% (man). These contractions were abolished by nifedipine, whereas Bay K 8644 significantly increased their amplitude, in rabbit preparations almost to control level. Electrical field stimulation produced contractions which could be suppressed by scopolamine by about 50% (rabbit) and more than 90% (man). These contractions were abolished by calcium-free medium (10(-4) M EGTA), suppressed by nifedipine, but significantly enhanced by Bay K 8644. The depressant effects of nifedipine, verapamil and diltiazem were reversed by Bay K 8644. The calcium channel blockers relaxed K+-induced contractions to base line, and this action was counteracted by Bay K 8644, less effectively when relaxations were induced by diltiazem. It is concluded that contractions produced by muscarinic receptor stimulation are primarily dependent on calcium bound to the outside of the membrane of the smooth muscle, and/or coming from the extracellular medium. Electrically evoked, scopolamine sensitive contractions seem to be mediated by a mechanism different from that of contractions produced by exogenously added muscarinic receptor agonist. The present data support the view that combined blockade of muscarinic receptors and calcium channels is an effective way of inhibiting bladder contractions in both rabbit and man.

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

Increase by oestrogen of calcium entry and calcium channel density in uterine smooth muscle.

1 The effect of in vivo oestrogen treatment on both 45Ca influx in myometrial strips and the kinetics of [3H)-nitrendipine binding in the isolated plasma membrane (PM) was studied. 2 After four days of continuous oestrogen treatment of ovariectomized rats, 45Ca influx in both resting (unstimulated) and K-stimulated myometrium was substantially increased. 3 Oestrogen treatment significantly increased the density in PM of nitrendipine binding sites and also caused a slight and insignificant increase in the affinity for nitrendipine. 4 The data suggest that the increase in Ca entry following oestrogen treatment probably results from an increase in calcium channel density.

Animals↗