The analysis of the relation between the molecular structure of drugs and their biological effects focuses on the structural characteristics of the drug that are recognized by receptors and on the possible molecular mechanisms that can lead to the tissue response. The basic assumption is that the interaction between drugs and receptors is dependent on the same molecular parameters that determine chemical interactions and reactions (1). On that basis, a description of drug-receptor interactions and mechanisms should follow the formal patterns of chemistry. Clearly the special parameters of biomolecular interactions, such as size and complexity of environment, determine a special class for these phenomena. Theoretical considerations as well as documented success in the study of biological interactions indicate, however, that these complex phenomena can be decomposed into physically meaningful steps that are amenable to analysis by methods of theoretical and quantum chemistry. A schematic representation of one possible form of
Gas chromatographic analysis showed acetylcholine to be the only choline ester released from innervated longitudinal muscle of the guinea pigileum by electrical stimulation. The amount of acetylcholine measured by gas chromatography agreed almost exactly with that measured by bioassay. Denervated longitudinal muscle produced no acetylcholine, and treatment of the muscle with tetrodotoxin markedly reduced acetylcholine output. The method permits the recovery and quantitation of amounts of acetylcholine as low as 5 nanograms in 5 milliliters of tissue perfusates.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicroanalytical determination of acetylcholine, other choline esters, and choline by pyrolysis-gas chromatographyP. I. A. Szilagyi, Dennis E. Schmidt, and Jack Peter. GreenCite this: Anal. Chem. 1968, 40, 13, 2009–2013Publication Date (Print):November 1, 1968Publication History Published online1 May 2002Published inissue 1 November 1968https://pubs.acs.org/doi/10.1021/ac60269a001https://doi.org/10.1021/ac60269a001research-articleACS PublicationsRequest reuse permissionsArticle Views152Altmetric-Citations73LEARN 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
Preparations of heparin, which have a greater amount of amino-containing compounds than can be accounted for as glucosamine, caused a contraction of the guinea pig ileum which was different in type from that induced by histamine and was not prevented by an antihistamine. The contraction was, in fact, similar to that observed with polypeptides. On hydrolysis of heparin (and of chondroitin sulfate and hyaluronate), histamine-like activity was evolved along with at least six ninhydrin-positive substances, including histidine. Histamine was demonstrated spectrofluorimetrically in the hydrolysates of bovine heparin. Under these conditions of hydrolysis, histamine was evolved from histidine, and this yield was greater when hydrolysis was carried out in the presence of heparin. It is concluded that preparations of heparin contain histidine and other ninhydrin-reacting materials besides glucosamine, and that at least some of these probably exist as a polypeptide(s), present as a contaminant. No evidence could be obtained for an enzymatic mechanism for producing histamine-like activity from preparations of heparin. Poly-L-lysylhistamine and two isoglucosides of histamine had no peptide-like action on the guinea pig ileum. Attempts to show the presence of substance P in neoplastic murine mast cells were unsuccessful, as were attempts to show the presence of significant amounts of bound histamine in these cells.
