PubMed Health⌕ Search

Biomedical subjects

N W Penn

Publications and source records attributed to N W Penn.

7 recordsLinked to original sources

Potentiation of morphine analgesic action in mice by beta-carotene.

beta-Carotene was found to potentiate morphine analgesia in hot plate experiments using mice. Response time was increased by about 100%, and the duration of analgesia was markedly prolonged. These features of beta-carotene were a function of the intact molecule, although the closely related compound, alpha-carotene, also exhibited this property. beta-Carotene alone had no effect on the nociceptive response. Other compounds with related structures, metabolic products, or anti-oxidants neither augmented nor antagonized morphine action.

Analgesics, Opioid↗

Deoxycytidine: a morphine antagonist.

Deoxycytidine antagonizes the analgesic action of morphine in the rat, morphine-induced respiratory depression in the rabbit and mitigates withdrawal in the dependent mouse. Administration of deoxycytidine does not precipitate the abstinence syndrome in dependent mice, a property shared by certain other endogenous morphine antagonsits. Cytidine and thymidine closely related in structure to deoxycytidine, are interchangeable with saline as controls, indicating a high degree of specificity in the receptor involved in the "action-effects" sequence. The requirement for deoxycytidine in countering the effects of morphine parallels the requirement for certain other DNA pyrimidines in the antagonism of barbiturate and alcohol. The rapidity of antogonist action suggests that such a DNA species would presumably be localized in the synaptosome, at outer membrane or the synaptic junction.

Analgesics, Opioid↗

Antagonism of barbiturate by DNA pyrimidines and allied compounds.

The mortality caused by barbiturate poisoning in mice is reduced by the combined action of the DNA pyrimidines thymine and 5-hydroxymethylcytosine (5-HMC) and the structurally related vitamins, pyridoxal, nicotinamide and thiamine, given intraperitoneally. The acute hypnotic effect of sodium pentobarbital at moderate to high dosages is also antagonized by these compounds. All five compounds are required for activity. The structural similiarity between these antagonist components and the barbiturates had suggested that the former's reactions as cofactors or as the constituents of more complex molecules might be points of drug inhibition. It therefore appeared that this inhibition might be reversed by administration of these cellular constituents. The obligatory requirement for both thymine and 5-HMC as components of this antagonist raises the possibility that a metabolically reactive DNA species in brain may be one site of barbiturate action. At the dosages employed, this antagonist produces no behavioral or symptomatic response in non-narcotized animals and may thus provide a basis for treatment of barbiturate poisoning.

Animals↗

The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid.

A method is given for small-scale preparation of DNA from 1.0-1.5g of adult rat tissues. The product from brain or liver is characterized by base ratios and phosphorus content which accord with reported values for rat tissue. It is reasonably free of RNA, protein and glycogen. It contains 5-hydroxymethylcytosine at a content of about 15% of the total cytosine bases present. 5-Hydroxymethylcytosine is also demonstrable in mouse and frog brain DNA and in the crude cytidylic acid fractions obtained from RNA hydrolysates of rat brain and liver. 5-Hydroxymethylcytosine is identified by paper chromatography, u.v. spectra in acid and alkaline solutions and by its conversion into 5-hydroxymethyluracil.

Animals↗

Quantitative determination of deoxyribonucleic acid in rat brain.

1. A procedure is given for spectrophotometric analysis of rat brain DNA after its resolution into component bases. Amounts of tissue in the range 50-100mg. can be used. 2. The amount of DNA obtained by the present method is 80% greater than that reported for rat brain by a previous procedure specific for DNA thymine. Identity of the material is established by the base ratios of purines and pyrimidines. The features responsible for the higher yield are the presence of dioxan during alkaline hydrolysis of tissue, the determination of the optimum concentration of potassium hydroxide in this step and omission of organic washes of the initial acid-precipitated residues. 3. The requirement for dioxan during alkaline hydrolysis suggests a possible association of brain DNA with lipid. The concentration of potassium hydroxide that gives maximum yield is 0.1m, indicating that there may be internucleotide linkages in this DNA that are more sensitive to alkali than those of liver or thymus DNA. 4. This procedure gives low yields of DNA from liver. It is not suitable for analysis of the DNA from this tissue.

Alkalies↗