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Biomedical subjects

B V Sastry

Publications and source records attributed to B V Sastry.

At least 37 records · Page 2Linked to original sources
PubMed1992

Characterization of the subtype of muscarinic receptor coupled to the stimulation of phosphoinositide hydrolysis in 132-1N1 human astrocytoma cells.

Stimulation of muscarinic receptors increases phosphoinositide (PI) hydrolysis in 132-1N1 human astrocytoma cells. To evaluate the subtype of receptors which mediate PI hydrolysis in 132-1N1 cells, the effects of: a) the nonselective M1 agonist, carbachol; b) the selective M1 agonist, 4-hydroxy-2-butynyl-trimethylammonium chloride-m-chlorocarbinilate (McN-343); c) the nonselective antagonists, atropine and scopolamine; d) the relatively selective M1 antagonist, pirenzepine; e) the relatively selective M2 antagonists, AF-DX 116 (11-2-diethylaminomethyl-1-piperidinylacetyl-5, 11-dihydro-6H-pyrido-2,3-b-1,4-benzodiazepine-6-one) and methoctramine and f) the relatively selective M3 antagonist, hexahydrosila-difenidol (HHSiD) on PI hydrolysis in 132-1N1 cells were studied. The cell pools of inositol-phospholipids were prelabelled by incubating 132-1N1 cells in a low inositol containing medium (CMRL-1066) supplemented with [3H]inositol (2 microCi/ml) for 20-24 hours at 37 degrees C. The cells were washed and resuspended in a physiological salt solution, and PI hydrolysis was measured by accumulation of [3H]inositol-1-phosphate (IP) in the presence of 10 mM LiCl. Carbachol produced time and concentration dependent PI hydrolysis (EC50, 37 microM). McN-A343 did not cause significant hydrolysis of PI in 132-1N1 cells indicating that the receptor was not of M1 type. All the above muscarinic antagonists caused a concentration dependent decrease in the level of IP in response to carbachol (100 microM). The rank order of their affinities (pA2 values) was: atropine (8.8) > HHSiD (7.6) > pirenzepine (6.8) > methoctramine (6.0) > AF-DX 116 (5.8). This rank order supports the concept that M3 (other names, M2 beta, glandular M2) receptors are linked to PI hydrolysis in 132-1N1 cells. HHSiD, which is selective for M3 receptors of the smooth muscle has higher affinity for muscarinic receptors in 132-1N1 cells than AF-DX 116 which is selective for M2 receptors in cardiac tissue. If the receptor in 132-1N1 cells had been M2, part of the rank order for affinities would have been methoctramine > AF-DX 116 > HHSiD > pirenzepine. From all of these observations, the muscarinic receptor for PI hydrolysis in 132-1N1 cells is tentatively characterized as of M3 type.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1991

Placental toxicology: tobacco smoke, abused drugs, multiple chemical interactions, and placental function.

There are increasing numbers of reports on the tobacco smoking and ingestion of abused drugs (e.g. morphine, cocaine) by pregnant women and the effects of the substances on the developing fetus and newborn infant. The passage of drugs and chemicals from the mother to the fetus is influenced by the placental transport and metabolism of the substances. Further, these drugs and chemicals affect the nutrient transport systems in the placenta. The three major drugs of abuse-nicotine, morphine and cocaine-depress both active amino-acid uptake by human placental villi and transplacental amino-acid transport by reason of the drugs' influence on placental cholinergic and opiate systems. Part of this depression (10-16%) is not reversible. Nicotine blocks the cholinergic receptor and thus blocks acetylcholine (ACh)-facilitated amino-acid transport. Morphine stimulates opiate kappa receptors and depresses ACh release. Cocaine blocks Ca2+ influx and thus blocks ACh release. ACh causes dilation of blood vessels and maintains placental blood flow by the activation of endothelial muscarinic receptors. By interfering with ACh release and placental blood flow, the three drugs of abuse may depress the diffusion of amino acids and other nutrients from the trophoblast into the placental circulation. Three regulatory systems are delineated for amino-acid uptake by the placenta: placental ACh, phospholipid N-methyltransferase, and the gammaglutamyl cycle. These systems operate in concert with one another and are dependent on cellular formation of adenosine 5'-triphosphate (ATP). Placental hypoxia induced by carbon monoxide and other tobacco gases depresses the energy-dependent processes and thus the ATP levels of placental cells. Maternal tobacco smoking and drug abuse cause placental insufficiencies for amino-acid transport, which may partially explain the fetal intrauterine growth retardation caused by these substances. Part of the amino-acid deficits may be compensated for by the induction of new amino-acid transport systems. Specific receptors or drug-binding proteins for the three drugs of abuse are present in the placenta. A DNA adduct selective for maternal smoking has been demonstrated in the placenta. DNA adducts selective for cocaine, morphine and other environmental chemicals have yet to be demonstrated ins the placenta.

Amino Acids↗
PubMed1991

Significance of substance P- and enkephalin-peptide systems in the male genital tract.

The plexi of the male reproductive tract have components of both the autonomic and sensory nervous systems. Rat epididymis was found to be a rich source of substance P. Substance P levels in the epididymis were higher by about 2.8 and 19.3 times than those in the prostate and seminal vesicles, respectively. Seminal vesicles were found to be a rich source of enkephalins. They had about 2.9 and 2.6 times higher leucine enkephalin levels than epididymis and prostate, respectively. Human seminal plasma contained about 47 times higher levels of leucine enkephalin than substance P. Using the split ejaculate technique, it has been demonstrated that early fractions of the human ejaculate contain fluids from prostate (and possibly epididymis), whereas later fractions represent seminal vesicle secretions. A low exogenous concentration of substance P (400 nM) increased sperm motility, whereas leucine enkephalin (100 microM) depressed it. Substance P (1-10 micrograms/mL) and muscarinic agonists enhanced the adrenergic transmission of the rat vas deferens to electrical stimulation. Leucine enkephalin (1-10 micrograms/mL) depressed adrenergic transmission and antagonized the effects of substance P and muscarinic agonists. These studies suggest that substance P-like tachykinins may play a role in sperm maturation, in expulsion of fluid from the epididymis, and in initiation of motility, whereas leucine enkephalin-like peptides may contribute to the orgasmic experience and detumescence.

Animals↗
PubMed1991

Halothane-induced alteration in the fluidity of rat brain synaptosomal membranes and its relationship to anesthesia.

Concentrations of halothane 1.43% or higher abolished the pain response and induced anesthesia. Halothane increased membrane fluidity of synaptosomes and microsomes both at non-anesthetic and anesthetic concentrations. Changes in fluidity in synaptosomes did not return to control levels even after the animals recovered from anesthesia. Alteration in membrane fluidity by halothane is a non-selective effect and may not play a definitive role in anesthesia.

Anesthesia↗
PubMed1990

Pancuronium, vecuronium, and d-tubocurarine inhibit and succinylcholine stimulates choline acetyltransferase activity.

The effects of the nondepolarizing muscle relaxants (NDMR), pancuronium, vecuronium, and d-tubocurarine and a depolarizing muscle relaxant, succinylcholine, were studied on choline acetyltransferase (ChAT) activity. A radiochemical assay was used in the determination of ChAT activity using purified placental enzyme. Pancuronium at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 3, 10, 15, 40 and 85 per cent, respectively; vecuronium at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 5, 10, 26 and 57 per cent, respectively; d-tubocurarine at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 0, 4, 12.5 and 29 per cent, respectively; whereas succinylcholine at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M activated ChAT activity by 8, 10, 1, and 2 per cent, respectively. Even though our present data demonstrated a significant dose-dependent inhibitory effect on ChAT activity by pancuronium, vecuronium and d-tubocurarine, it is unlikely that this inhibitory effect will contribute to the mechanism of action of NDMR. Our data, however, may suggest an additional mechanism for the phenomena of tetanic and train-of-four fades that are seen following the administration of nondepolarizing muscle relaxants.

Carbon Radioisotopes↗
PubMed1990

In vitro effects of fluoride and bromide on pseudocholinesterase and acetylcholinesterase activities.

The in vitro effects of two metabolites of inhalational anaesthetics, fluoride and bromide, on pseudocholinesterase (PCHE) and acetylcholinesterase (ACHE) activities in the blood samples of seven healthy patients were studied. The PCHE and ACHE activities were determined by kinetic spectrophotometric methods. Fluoride at the levels achieved with clinical concentrations of enflurane and sevoflurane (25-75 microM.L-1) inhibited PCHE activity by 28-65 per cent (P less than 0.01) and ACHE activity by less than five per cent (P greater than 0.05). Bromide at the levels achieved with clinical concentrations of inhalational anaesthetics had no significant effect on either PCHE or ACHE activity. We recommend caution when succinylcholine and/or ester type local anaesthetics are used in the immediate postoperative period following enflurane or sevoflurane anaesthesia. We also recommend that blood drawing for PCHE activity be delayed at least until 24 hr following enflurane or sevoflurane anaesthesia.

Acetylcholinesterase↗
PubMed1990

Halothane and isoflurane alter phospholipid transmethylation in rat brain synaptosomes.

The mechanism of action of inhalational anesthetics is unknown, but neuronal membrane alteration is a favored hypothesis. Since phospholipid methylation and translocation play a key role in the transmission of biologic signals across cell membranes, we examined the effect of two commonly used halogenated anesthetics, halothane and isoflurane, on phospholipid methylation in rat brain synaptosomes. Using S-adenosyl-L-[3H-methyl]methionine as a donor, we found a two-fold increase in 3H-methyl incorporation into phospholipids in synaptosomes taken from rats exposed to concentrations that just abolish pain response, but not in rats exposed to higher or lower concentrations. Methylation was not increased in rats newly recovered from anesthesia. Halothane added to synaptosomes taken from rats not previously exposed to anesthetics stimulated 3H-methyl incorporation over a wide range of concentrations. Enhancement of phospholipid methylation by halothane and isoflurane may effect an alteration of neural signal transduction that results in the anesthetic state.

Animals↗
PubMed1990

Substance P, acetylcholinesterase, and beta-endorphin levels in the plasma and pericardial fluid of patients with and without angina pectoris.

We measured substance P-like immunoreactivity (SPLI), beta-endorphin-like immunoreactivity (BELI), acetylcholinesterase activity, and total protein content in pericardial fluid and plasma of patients with angina pectoris and patients with no angina pectoris. SPLI and BELI levels, acetylcholinesterase activity, and total protein content were determined by radioimmunoassay, a colorimetric method, and by the method of Lowry et al. (J Biol Chem 1951; 193:265-75), respectively. In the pericardial fluid, patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 1.69 +/- 0.23 fmol/mg protein, 0.16 +/- 0.13 fmol/mg protein, 0.06 +/- 0.02 units, and 25.7 +/- 3.2 mg/ml, respectively. Patients with no angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.93 +/- 0.17 fmol/mg protein, 0.19 +/- 0.10 fmol/mg protein, 0.16 +/- 0.02 units, and 44.6 +/- 5.3 mg/ml, respectively. SPLI levels were significantly higher (p less than 0.03), and acetylcholinesterase (less than 0.002) and total protein content (less than 0.004) were significantly lower in the pericardial fluid of patients with angina when compared with those of patients with no angina. BELI levels were not significantly different between the two groups. In the plasma, no significant differences were found in SPLI, BELI, acetylcholinesterase, and total protein values between the two groups of patients. Patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.47 +/- 0.26 fmol/mg protein, 0.06 +/- 0.06 fmol/mg protein, 0.29 +/- 0.15 units, and 68.2 +/- 8.7 mg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1989

Pseudocholinesterase activity in human cerebrospinal fluid.

Pseudocholinesterase (PCHE) activity and dibucaine numbers (DN) in the cerebrospinal fluid (CSF) and plasma of 10 ASA physical status 1 and 2 patients were measured using a kinetic method. CSF had a mean PCHE activity of 0.018 +/- 0.013 unit/ml with a DN of 59 +/- 4. Whereas, PCHE activity and DN in the plasma were 0.960 +/- 0.12 units/ml and 84 +/- 3, respectively. We also measured PCHE activity and DN in the CSF and plasma of 4 patients in whom there was a recent history of intraventricular bleeding. These patients had a CSF PCHE activity of 0.340 +/- 0.07 units/ml (DN = 78 +/- 3) and a plasma PCHE activity of 0.950 +/- 0.10 units/ml (DN = 82 +/- 2). Our data show that there is a low activity of PCHE in CSF, 1/20-1/100th that of plasma. Our data also show that PCHE activity increased to 1/4 to 1/2 that of plasma in CSF of patients with bleeding into CSF.

Adult↗
PubMed1988

The inhibitory effect of metoclopramide on plasma cholinesterase activity.

The in vitro effect of metoclopramide on plasma cholinesterase (PCHE) activity was studied to investigate a mechanism for metoclopramide-induced prolongation of succinylcholine action. The mean PCHE of the control samples was 0.86 +/- 0.02 unit.ml-1. PCHE activity in the presence of metoclopramide, at concentrations of 0.05, 0.10, 0.50, 1.0, 2.5 and 5.0 micrograms.ml-1, was reduced to 0.78 +/- 0.02, 0.69 +/- 0.04, 0.50 +/- 0.03, 0.39 +/- 0.02, 0.24 +/- 0.01 and 0.15 +/- 0.01 unit.ml-1, respectively. Our data demonstrated that PCHE activity was significantly depressed by metoclopramide at all concentrations studied (p less than 0.001). Our data also show that the concentration of metoclopramide required to inhibit 50 per cent of PCHE activity (I50) was 0.8 micrograms.ml-1 (2.4 x 10(-6) M). We recommend caution when succinylcholine and or ester type local anaesthetics are administered to patients who are also receiving metoclopramide, especially in high doses.

Adult↗
PubMed1988

Relationships between chemical structure and inhibition of choline acetyltransferase by 2-(alpha-naphthoyl)ethyltrimethylammonium and related compounds.

A choline acetyltransferase (ChA) inhibitor with an optimum combination of properties of potency, stability and membrane permeability is required to study several functional aspects of acetylcholine in nervous and non-nervous tissues. Therefore, 2-(alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA), 2-(beta-naphthoyl)ethyltrimethylammonium iodide (beta-NETA), 2-(9'-anthroyl)ethyltrimethylammonium iodide (9'-AETA) and their corresponding tertiary dimethylamine hydrochloride analogs (alpha-NEDA, beta-NEDA, 9'-AEDA) were synthesized and tested for their ChA inhibitory activities. The quaternary ammonium compounds were more potent inhibitors (150 in microM: alpha-NETA, 9; beta-NETA, 76; 9'-AETA, 32) than the corresponding tertiary compounds (150 in microM: alpha-NEDA, 63; beta-NEDA, 1400; 9'-AEDA, 77). The alpha-naphthyl moiety was preferable to the beta-naphthyl- or 9'-anthryl moieties for alignment with the enzyme for inhibition. alpha-NETA and alpha-NEDA exhibited adequate ChA inhibitory potencies for further pharmacological studies and localization of membrane bound ChA. They exhibited fluorescent characteristics of the alpha-naphthyl moiety. Their ChA inhibition was not reversible by dialysis. They were considerably more potent for inhibiting ChA than cholinesterases and carnitine acetyltransferase.

Acetylcholine↗
PubMed1988

2-(alpha-Naphthoyl)ethyltrimethylammonium iodide and its beta-isomer: new selective, stable and fluorescent inhibitors of choline acetyltransferase.

The activities of 2-(alpha-naphthoyl)ethyltrimethylammonium (alpha-NETA) and its beta-isomer (beta-NETA) were studied at various sites of the cholinergic system using isolated enzyme and organ systems. They were selective inhibitors (I50: alpha-NETA, 9 microM; beta-NETA, 76 microM) of choline acetyltransferase (ChA). The inhibition of ChA by both alpha- and beta-NETA was noncompetitive with acetylcoenzyme A or choline as the variable substrate. In these experiments, the inhibitor and both substrates were added simultaneously to the reaction medium, and short reaction times of 10 min were used to determine initial linear velocities. Under these experimental conditions in the presence of substrates, the degree of inhibition of ChA by alpha-NETA was independent of enzyme concentration indicating the reversibility of the inhibition. If ChA was incubated with alpha-NETA for 10 min in the absence of substrates, the degree of inhibition was higher and was not reversible by dialysis of the inhibited ChA. These observations indicate that alpha-NETA is a pseudo-reversible or slowly reversible inhibitor. Neither alpha- nor beta-NETA exhibited significant effects at muscarinic receptors, ganglionic nicotinic receptors, skeletal muscular nicotinic receptors, cholinesterases or carnitine acetyltransferase at concentrations which inhibited ChA. At concentrations higher than their I50 values to inhibit ChA, both antagonized the effects of acetylcholine (ED50: alpha-NETA, 70-80 microM; beta-NETA, 100 microM), histamine and KCl-induced contractions in the guinea pig longitudinal ileal muscle. At high concentrations, alpha-NETA activated acetylcholinesterase (EC50, 360 microM) and inhibited cholinesterase (EC50, 1100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A↗
PubMed1988

Maternal tobacco smoking and alterations in amino acid transport in human placenta: induction of transport systems.

The uptake of 14C-alpha-aminoisobutyric acid (AIB) by human placental villi from smokers and nonsmokers was measured. Washed placental villi of smokers exhibited higher uptake capacity for AIB than those of nonsmokers. The higher uptake capacity in smokers was due to increase in Vmax. Smoking increased Km and decreased affinity to AIB. This is possibly due to decreased fluidity of the plasma membrane of the villus during maternal smoking. These observations suggest that placenta utilizes its ability to increase the accumulation of amino acids during the adverse environmental conditions produced by maternal smoking.

Aminoisobutyric Acids↗
PubMed1987

The effect of procainamide on plasma cholinesterase activity.

The in vitro effect of procainamide on plasma cholinesterase (PCHE) activity in the plasma of ten normal ASA physical status I patients was studied using a kinetic method. The mean plasma cholinesterase activity without procainamide (control) was 0.90 +/- 0.09 units.ml-1. The dibucaine numbers of all the samples were in the normal range of 78 to 86, indicating normal genotypes. The mean plasma cholinesterase activity, in the presence of procainamide in concentrations of 5.0, 10.0, 20.0 and 40.0 micrograms.ml-1, was reduced to 0.73 +/- 0.04, 0.61 +/- 0.03, 0.45 +/- 0.02, and 0.36 +/- 0.01 units.ml-1, respectively. At therapeutic concentrations of 4 to 12 micrograms.ml-1, procainamide inhibited cholinesterase activity 15 to 30 per cent. The authors also showed that the concentration of procainamide required to inhibit 50 per cent of plasma cholinesterase activity was 20 micrograms.ml-1 (I50). The authors conclude that procainamide when tested in vitro had a statistically significant depressant effect on plasma cholinesterase activity at all the concentrations studied.

Adult↗
PubMed1987

Effect of pre-eclampsia on plasma cholinesterase activity.

Plasma cholinesterase (PCHE) activity was determined using a colorimetric method in 11 healthy non-pregnant women, 11 healthy pregnant women at term, and 11 pre-eclamptic pregnant women at term. The mean plasma cholinesterase activities for healthy non-pregnant women, healthy pregnant women and pre-eclamptic pregnant women were 438 +/- 81,257 +/- 25 and 173 +/- 18 units . ml-1, respectively. Our data suggest that there is a significant reduction in plasma cholinesterase activity in preeclamptic pregnant women when compared to healthy non-pregnant (p less than 0.001) and healthy pregnant women (p less than 0.001).

Adolescent↗
PubMed1987

Activities of 5-methylfurfuryltrimethylammonium iodide and related compounds at vascular endothelial muscarinic receptors of the rat aorta.

5-Methylfurfuryltrimethylammonium iodide (5-MFT) is a furan analog of muscarine and was studied for its cholinergic activity at vascular endothelial receptors of the rat aorta. Other related compounds have different substitutions at position 5 of the furan ring and include the following compounds: 5-hydroxymethyl- (5-HMFT), 5-chloromethyl- (5-CMFT), 5-bromomethyl- (5-BMFT), 5-iodomethyl- (5-IMFT), and 5-methoxy- (5-MOFT) furfuryltrimethylammonium salts. The furan analogs relaxed helical strips of rat aorta which contracted with norepinephrine (10(-6)M). These relaxations were endothelial cell-dependent. The ED50's for muscarinic activities increased in the following order: 5-MFT = ACh less than dl-muscarine less than 5-HMFT = 5-CMFT less than 5-MOFT less than 5-BMFT less than 5-IMFT. Among the furan analogs, 5-MFT was found to be a full agonist at the endothelial cells; other furan analogs were only partial agonists. The affinities and relative intrinsic efficacies of the most potent analogs decreased in the following order: ACh = 5-MFT greater than dl-muscarine greater than 5-HMFT greater than 5-CMFT. Atropine and scopolamine antagonized relaxations by furan analogs. KB values for atropine and scopolamine against ACh, 5-MFT or 5-HMFT as agonist were not different, indicating that these agonists and antagonists were acting at the same muscarinic receptors. The KB of atropine and of scopolamine increased when 5-CMFT was used as an agonist, indicating that 5-CMFT may cause relaxation by acting at other sites besides endothelial muscarinic receptors. The endothelial muscarinic receptor might be classified tentatively as of M2 or Ms type. These studies did not exclude the possible heterogeneity of the endothelial muscarinic receptors.

Animals↗
PubMed1986

Effect of L-methionine on contractile response, calcium influx and calcium channel blocking agents in the rat aorta.

L-Methionine incubated with aorta strips and S-adenosyl-L-methionine incubated with aorta membranes methylate membrane phospholipids. L-Methionine enhances the contractile response of helical strips of rat aorta to KCl. L-Methionine also enhances the slow component of the contractile response of rat aorta to norepinephrine associated with influx of exogenous calcium. L-Homocysteinethiolactone inhibits methylation of membrane phospholipids and depresses the contractile response to KCl and to norepinephrine. L-Methionine enhances and L-homocysteinethiolactone depresses KCl-stimulated influx of calcium into rat aorta strips. L-Methionine has no effect on calcium efflux. Tested against calcium channel blocking agents, L-methionine reduces the inhibition caused by diltiazem and chlorpromazine but not that caused by TMB 8 or verapamil. It is postulated that methylated intermediates of phospholipid methylation enhance the function of membrane calcium channels.

Animals↗