In an effort to investigate the possibility of noncholinergic nicotine sites within the brain, psychopharmacological, biochemical and eletrophysiological studies were undertaken with nicotine and various newly synthesized derivatives of nicotine and piperidine. When 1-10 micrograms of (-)-nicotine was injected into the region of the lateral ventricle of rats through implanted cannulae, there resulted a characteristic prostration immobilization syndrome, which was accompanied by seizures and tremors at the higher dose range. The (+)-isomer possessed 1/100 the activity of the natural (-)-isomer. The syndrome could be prevented by pre-treatment, intraventricularly, with the N-benzyl and N-p-nitrophenylazido derivates of either nicotine or piperide. A variety of neurotransmitters and psychotropic agents, including acetylcholine and anticholinergic drugs, were without antagonistic action. After nicotine, recordings of spontaneous electrical activity from electrodes chronically implanted into the region of the dorsal hippocampus showed a marked decrease in the amplitude and number of 6-8 sec discharges, and the change was correlated with the behavioral syndrome. Receptor binding studies were performed with rat brain slices and various neural preparations using 3H-nicotine, 125I-alpha-bungarotoxin and 14C-d-tubocurarine as ligands; and only with 3H-nicotine was it possible to demostrate any competitive effect with the various nicotine and piperidine antagonists. It was possible to demonstrate stereospecific or specific nicotine binding to only glass fiber filters and, to a lesser extent, brain slices, but not to cell-free preparations. It was concluded that there existed specific noncholinergic sites for nicotine's action which have not been hitherto described.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on the Synthesis of Insulin from Natural and Synthetic A and B Chains. I. Splitting of Insulin and Isolation of the S-Sulfonated Derivatives of the A and B Chains*Panayotis G. Katsoyannis, Andrew Tometsko, Clyde Zalut, Stanley Johnson, and Anthony C. TrakatellisCite this: Biochemistry 1967, 6, 9, 2635–2642Publication Date (Print):September 1, 1967Publication History Published online1 May 2002Published inissue 1 September 1967https://pubs.acs.org/doi/10.1021/bi00861a001https://doi.org/10.1021/bi00861a001research-articleACS PublicationsRequest reuse permissionsArticle Views174Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Abstract Chemical risk assessment has been limited by the inability of in vitro short‐term assays to identify the true carcinogenic potential of many substances. Numerous methods exist for identifying mutagenic and clastogenic agents, but a practical means of identifying nongenotoxic carcinogens has remained elusive. Experiments described here suggest that some chemicals may participate in carcinogenesis by modulating the enzymatic processes of drug metabolism. The tumor promoters butylated hydroxyanisole, butylated hydroxytoluene, deoxycholic acid, reserpine, trypan blue, and 12,‐O‐tetradecanoyl phorbol‐13‐acetate were chosen as model non‐genotoxic carcinogens. The enzyme‐modulating action of these chemicals was measured using a modified Ames plate incorporation assay whereby the known tumor promoters were plated with a promutagen in the presence of a mammalian metabolic activation system (S9). Each of the nongenotoxic carcinogens significantly increased the mutagenic response of metabolically activated promutagen(s). These experiments suggest that the carcinogenic role of some chemicals may be attributed to their ability to modify the biochemical pathways of drug metabolism. By enhancing or inhibiting the activity of various enzymes, some tumor promoters may create an environment that increases a cell's mutational burden, thereby contributing to neoplastic transformation.
Instrumentation for the automated chemical synthesis of polypeptides controlled by computer generated paper tape programs is described. The automatic chemical reaction system (ACRS) translated binary coded commands from the paper tape into physical operations resulting in the synthesis of a model polypeptide. The commands for the entire synthesis were generated by computers. Using our computer programs for the synthesis of polypeptides, it is necessary only to specify the amino acid sequence and the computer will set up the appropriate sequence of physical operations (wash cycles, stirring, filtration steps, amino acid additions, etc.) to carry out the synthesis of the desired amino acid sequence. The computer could also automatically make adjustments in the synthetic approach to accommodate the unique problems involved in coupling different amino acids.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInsulin peptides. XVII. Synthesis of the A chain of human (porcine) insulin and its isolation as the S-sulfonated derivativePanayotis G. Katsoyannis, Andrew M. Tometsko, and Clyde. ZalutCite this: J. Am. Chem. Soc. 1967, 89, 17, 4505–4513Publication Date (Print):August 1, 1967Publication History Published online1 May 2002Published inissue 1 August 1967https://pubs.acs.org/doi/10.1021/ja00993a046https://doi.org/10.1021/ja00993a046research-articleACS PublicationsRequest reuse permissionsArticle Views78Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
