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Biomedical subjects

W R McConnell

Publications and source records attributed to W R McConnell.

4 recordsLinked to original sources
PubMed1979

Reduction of glutathione levels in livers of mice treated with N,N'-bis (2-chloroethyl)-N-nitrosourea.

N-methyl-N-nitrosourea (MNU), N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea (methylCCNU), and N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) were examined for their effect on glutathione (GSH) levels of various tissues of normal and L1210-leukemic mice. BCNU produced significant decreases in the GSH levels of livers of both groups, but caused no change in the GSH content of the L1210 tumor or in the lungs. The GSH content of the kidneys of L1210 tumor-bearing mice, however, was significantly decreased by BCNU at early time points. A small increase in the liver content of oxidized glutathione could not account for the decrease content of GSH. Methyl CCNU and MNU were without effect on any of the tissues examined. These data are consistent with our previous observation that BCNU is a substrate for GSH S-transferase, and suggest that a GSH-dependent process is an important pathway for the metabolism of BCNU.

Animals↗
PubMed1978

A study of the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on mammalian salivary flow.

delta 9-Tetrahydrocannabinol (delta 9-THC) caused no change in either pilocarpine or acetylcholine (ACh)-stimulated salivary flow of the cat but significantly decreased salivary flow from the submaxillary gland of the car and dog during electrical stimulation of the chorda tympani. In contributing to this effect, delta 9-THC significantly decreased (47%) basal arterial blood flow to the submaxillary gland of the dog and markedly reduced (51%) the stimulated blood flow to the gland produced by electrical stimulation of the chorda tympani. The decrease in stimulated blood flow by delta 9-THC suggested an effect on the ACh of the gland. No decrease in the synthesis of ACh could be demonstrated in the submaxillary gland of the dog. A significant decrease (37%) in the release of ACh from transmurally stimulated guinea-pig ileum, a model tissue, was produced by delta 9-THC. These data suggest that delta 9-THC decreases electrically stimulated salivary flow by a mechanism involving the decrease in release of ACh which results in a reduction of blood flow to the submaxillary gland, and, also, less ACh for stimulation of the secretory cells of the gland.

Acetylcholine↗
PubMedDate not supplied

Pharmokinetics of 2'-deoxycoformycin in normal and L1210 leukemic mice.

Following intravenous administration, 2'-deoxycoformycin (0.25 mg/kg) was rapidly distributed to tissues of both normal mice and mice bearing L1210 leukemia cells and readily eliminated, primarily by urinary excretion. Elimination of 2'-deoxycoformycin from plasma was biphasic, and half-lives for the alpha- and beta-phases of 10 and 33 min for normal mice and 7 and 40 min for L1210-bearing animals. The volume of distribution at steady state was approximately 20 ml, suggesting that the drug was distributed in the total body water for both groups of mice. The kidney, liver, small intestine, spleen, thymus, and L1210 tumor had tissue/plasma ratios greater than or equal to 1 at 15 min after dosing. In both groups, greater than 90% of the dose of 2'-deoxycoformycin was recovered in the urine within 3 hr. As determined by bioautography of urine samples, no detectable metabolism occurred. The presence of the L1210 tumor caused changes in the tissue distribution of 2'-deoxycoformycin. At later time periods, tissues from tumor-bearing mice contained significantly higher levels of this drug when compared to normal mice. However, the tumor was without significant effect on blood levels or urinary excretion of 2'-deoxycoformycin.

Animals↗