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Biomedical subjects

B V Sastry

Publications and source records attributed to B V Sastry.

At least 73 records · Page 4Linked to original sources
PubMed1979

Formation of alpha-methyldopamine ("Catecholamphetamine") from p-hydroxyamphetamine by rat brain microsomes.

Amphetamine is a sympathomimetic and psychotropic drug which is extensively metabolized in liver and in brain. One of its major metabolites, p-hydroxyamphetamine, is accumulated by cortical and striatal synaptosomes. In order to learn whether p-hydroxyamphetamine can be further metabolized to a catecholamine, a sensitive radioenzymatic assay was developed which couples the formation of the "catecholamphetamine" to rapid O-methylation by catechol-O-methyltransferase in the presence of [3H]-methyl-S-adenosylmethionine. Rat brain microsomes contain a cytochrome P-450-dependent monooxygenase which synthesizes catecholamphetamine from p-hydroxyamphetamine. The formation of this catechol metabolite may be involved in the development of tolerance in chronic amphetamine use.

Amphetamines↗
PubMed1978

Relationships between chemical structure and inhibition of human placental choline acetyltransferase by keto analogs of acetylcholine.

Seven keto analogs of acetylcholine were synthesized and evaluated as inhibitors of human placental choline placental choline acetyltransferase. Their potencies for inhibition of horse serum cholinesterase and stimulation of cholinergic receptors in the longitudinal ileal muscle of the guinea pig were investigated. The most potent and selective inhibitor of choline acetyltransferase was (2-benzoylethyl)trimethylammonium chloride with an I50 of 3 X 10(-6) M. It exhibited considerably low activities at muscarinic and nicotinic receptors and cholinesterases. Its high potency for inhibiting choline acetyltransferase was atrributed to: (a) its cationic terminal, a site for an electron acceptor interaction; (b) an aryl moiety for hydrophobic and electron donor contributions; and (c) a positive charge on the carbon atom adjacent to the benzene ring due to the presence of the carbonyl group, which interacts with the nucleophilic residue on the enzyme.

Acetylcholine↗
PubMed1978

Effects of cooling on the levels of acetylcholine, cholinesterase, choline acetyltransferase and the intramural electrical stimulation on the guinea pig ileum.

The effects of hypothermia (4 degrees C) on the components of the cholinergic system of the ileal longitudinal muscle and the adherent Auerbach's plexus of the guinea pig ileum have been investigated. Acetylcholine (ACh) content of the muscle was determined by pyrolysis-gas chromatography. It decreased from 119 to a fairly steady level of 16 nmol/g of wet tissue during the first 72 h of cold storage at 4 degrees C under anoxic conditions. Concomitantly, responsiveness to intramural electrical stimulation decreased by 72%. Cholinesterase (ChE) and choline acetyltransferase (ChA) activities each dropped by 40% during this period. However, the de novo synthesis of ACh over the period of study did not change significantly. The response of the preparation to the exogenously applied ACh remained fairly constant suggesting that the changes in the cholinergic receptor are not accountable for the decrease in responsiveness to intramural stimulation. From the results of this study, it has been concluded that cold storage for 5 days leads to: (1) a significant decline in ACh content within 72 h of storage; (2) a decrease in ChE and ChA activities; (3) no significant effect on the cholinergic receptor; and (4) a decrease in responsiveness to intramural electrical stimulation which is probably due to a malfunction of the ACh-releasing mechanism.

Acetylcholine↗
PubMed1978

(2-Benzoylethyl)trimethylammonium chloride: a new, selective and stable inhibitor of human placental choline acetyl transferase.

(2-Benzoylethyl)trimethylammonium chloride (BETA), a keto analog of acetylcholine, was synthesized and studied as an inhibitor of human placental choline acetyltransferase (ChA). It is a potent inhibitor of ChA with an 150 of 3.1 X 10(-6) M. The inhibition was rapid in onset and was slowly reversible. Upon dialysis of the inhibited ChA, 50% activity was recovered within about 4.90 hours. BETA was noncompetitive with respect to both substrates of ChA, acetyl-CoA and choline. BETA was selective for inhibiting ChA. It was about 100, and 50, times more potent for inhibiting ChA than acetylcholinesterase, and cholinesterase, respectively. Its activities at muscarinic and nicotinic receptors were negligible at the concentrations where complete inhibition of ChA was obtained. In contrast to the other ChA inhibitors, the styrylpyridines and halogenoacetylcholines, BETA is stable in solution. On prolonged storage (several days at 37 degrees C and pH 7.4), solutions of BETA decomposed partially into trimethylamine and vinylphenylketone. Beta was considerably more stable and more selective than other inhibitors of ChA.

Acetylcholine↗
PubMed1978

Dithiothreitol-induced alterations of blood pressure, vascular reactivity and aortic microsomal calcium uptake in spontaneously hypertensive rats.

Dithiothreitol, a potent sulfhydryl reducing agent, depressed systolic blood pressure to a greater extent in genetically hypertensive rats (SHR) than in normotensive Wistar-Kyoto rats (WKY). Dithiothreitol depressed the contractile response to norepinephrine and potassium chloride of isolated aortic strips from both SHR and WKY. Dithio-bis-2-nitrobenzoid acid, a sulfhydryl oxidizing agent, restored the responsiveness of rat aortic strips to these contractile agents. Microsomes isolated from rat aortae sequester calcium in the presence of ATP. This activity, generally referred to as calcium-pump activity, has been postulated to function in smooth muscle relaxation, and is significantly depressed in aortic microsomes of the SHR. Dithiothreitol (10 mM) greatly increased and dithio-bis-2-nitrobenzoic acid (100 micrometer) decreased the ATP-dependent calcium pump activity of microsomes isolated from both SHR and WKY aortae. These observations indicate that sulfhydryl groups may influence systems involved in vascular reactivity and blood pressure regulation.

Animals↗
PubMed1977

Identification of acetylcholine and propionylcholine in bull spermatozoa by integrated pyrolysis, gas chromatography and mass spectrometry.

Acetylcholine was identified in fertile bull spermatozoa using combined pyrolysis gas-chromatography and mass spectrometry. Bull spermatozoa contain other minor choline esters in smaller quantities than acetylcholine. One of the minor choline esters is possibly propionylcholine. The spermatozoa from infertile bulls exhibited low motility and very low levels of acetylcholine.

Acetylcholine↗
PubMed1977

Distribution and pharmacokinetics of triamterene in rats.

The tissue distribution of 14C-triamterene was examined in the fact. After intravenous administration of 14C-triamterene, high concentration ratios between tissues and blood were found in most tissues except the brain, fat, and testes. The maximal concentration of the drug was in the kidneys, liver, heart, lungs, and skeletal muscle within the first 20 min, when the maximal natriuresis was observed. No metabolite of triamterene was detected in these tissues. The pharmacokinetics of 14C-triamterene also were investigated. The volume of distribution of the drug was greater in the central compartment (60% of the dose) than in the peripheral compartment (40%). The binding of the drug to skeletal muscle is responsible for the fraction of the dose in the peripheral compartment. Rate constants indicate that slow elimination of triamterene is related to its binding to tissue in the central compartment.

Animals↗
PubMed1977

Relationships between the chemical structure and pharmacological activities of D(-)S-and L(+)R-tropinoylcholines at cholinergic sites.

D(-)S-and L(+)R-tropinoylcholines were synthesized and their antagonisms to acetylcholine (ACh) were studied at muscarinic receptors (guinea-pig longitudinal ileal muscle), acetylcholinesterase (AChE) and pseudocholinesterase (ChE). Tropinoylcholines were reversible competitive antagonists at muscarinic receptors. D(-)S-tropinoylcholine exhibited a higher affinity as an antagonist at muscarinic receptors than the L(+)R-isomer. ONE MOLECULE OF THE ANTAGONIST COMPETES WITH ONE MOLECULE OF THE AGONIST AT EACH MUSCARINIC RECEPTOR SITE. Tropinoylcholines were competitive inhibitors of AChE. L(+)R-tropinoylcholine exhibited a lower K1 and a higher affinity for AChE. Therefore, muscarinic receptors were stereospecific for the D-configuration, whereas AChE was stereospecific forthe L-configuration of tropinoylcholine. Tropinoylcholines were week agonist at nicotinic receptors (frog rectus abdominis); they were substrates of ChE at low concentrations, but they inhibited ChE partially at high concentrations. L(+)R-tropinoylcholine had a lower apparent Km and a higher affinity than its isomer. Therefore, the esteratic site of ChE is possible stereospecific for the L-configuration of tropinoylcholine. Both tropinoylcholines were mixed inhibitors (competitive and noncompetitive) of ACh hydrolysis by ChE. The results imply that the tropinoylcholines interact at a second site as well as the esteratic site.

Acetylcholine↗
PubMed1977

Effects of nicotine and cocaine on the release of acetylcholine from isolated human placental villi.

According to our studies, human term placenta contains about 112 nmol/g of ACh. In the present studies, isolated placental villi were suspended in Kreb's bicarbonate buffer (pH 7.4) at 37 degrees and acetylcholine (ACh) released into the medium was analyzed by gas chromatography. The spontaneous release of ACh into the medium was linear with time and was 35 pmol/g/min. Cocaine in doses of 280 and 56o micrometer decreased the spontaneous release of ACh to 23, and 17 pmol/g/min, respectively. Raising the Ca2+ concentration in the Kreb's bicarbonate buffer from 2.34 to 4.64 mM, or the addition of nicotine (58 micrometer) to the bath increased the rate of release of ACh to 53 and 47 pmol/g/min, respectively. Cocaine decreased the rate of release of ACh even in the presence of Ca2+ or nicotine. ACh was not released when Ca2+ was absent in the medium. Nicotine did not stimulate the release of ACh in the Ca2+ free medium. High concentrations of K+ increased ACh release in the presence of Ca2+ and it did not have any effect on ACh release in the absence of Ca2+. These observations indicate that external Ca2+ is required for the release of ACh and cocaine acts possibly by preventing the entry of external Ca2+ into the syncytiotrophoblast, and thereby decreases ACh release from the placental villus.

Acetylcholine↗
PubMed1976

Synthesis of N,N'-bis(3-substituted benzylideneaminopropyl)-piperazines and their anti-inflammatory, antiproteolytic, and anticonvulsant properties.

Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to 67%. The antiproteolytic activity of these piperazines was reflected by their ability to inhibit in vitro hydrolysis of bovine serum albumin and casein by trypsin. The inhibition of trypsin-induced hydrolysis was concentration dependent and competitive in nature.

Animals↗
PubMed1976

CNS depressant activity of pyrimidylthiazolidones and their selective inhibition of NAD-dependent pyruvate oxidation.

Several 1-aryl-3-(2-pyrimidyl)thiocarbamides and their corresponding cyclized 2-arylimino-3-(2-pyrimidyl)thiazolid-4-ones were synthesized and characterized by their sharp melting points and elemental analyses. These thiocarbamides and thiazolidones possessed anticonvulsant activity against pentylenetetrazol-induced convulsions and potentiated pentobarbital-induced hypnosis in mice. Most of these thiocarbamides and thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, where the use of added NAD dether hand, remained unaltered. The anticonvulsant activity of thiocarbamides and thiazolidones was unrelated to their ability to inhibit the respiratory activity of rat brain homogenates during oxidation of sodium pyruvate. Cyclization of thiocarbamides to the corresponding thiazolidones in general enhanced their CNS depressant and enzyme inhibitory effectiveness.

Animals↗