| Subject | Predicate | Object | Context |
|---|---|---|---|
| pubmed-article:9658581 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9658581 | lifeskim:mentions | umls-concept:C0598333 | lld:lifeskim |
| pubmed-article:9658581 | lifeskim:mentions | umls-concept:C0039808 | lld:lifeskim |
| pubmed-article:9658581 | lifeskim:mentions | umls-concept:C0597358 | lld:lifeskim |
| pubmed-article:9658581 | lifeskim:mentions | umls-concept:C1510827 | lld:lifeskim |
| pubmed-article:9658581 | lifeskim:mentions | umls-concept:C0336791 | lld:lifeskim |
| pubmed-article:9658581 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:9658581 | pubmed:dateCreated | 1998-7-23 | lld:pubmed |
| pubmed-article:9658581 | pubmed:abstractText | Determination of drug-receptor binding constants (association, KA, or dissociation, KD = l/KA) by radiochemical specific binding assays has proved to be an invaluable tool for screening of potential active drugs. Simple determination of KA (or KD) values makes it possible, however, to calculate the standard free energy delta G degree = -RTln KA = RTln KD (T = 298.15 K) of the binding equilibrium but not that of its two components as defined by the Gibbs equation delta G degree = delta H degree - T delta S degree, where delta H degree and delta S degree are the equilibrium standard enthalpy and entropy, respectively. This incomplete knowledge is highly inconvenient from a pure thermodynamic point of view as delta H degree and delta S degree carry much information on the details of the drug-receptor interaction and the interplay of both reaction partners with the solvent. In recent times it has been shown that the relative delta H degree and delta S degree magnitudes can often give a simple 'in vitro' way for discriminating 'the effect', that is the manner in which the drug interferes with the signal transduction pathways. This particular effect, called 'thermodynamic discrimination', results from the fact that binding of antagonists may be enthalpy-driven and that of agonists entropy-driven, or vice versa. The first case of thermodynamic discrimination was reported for the beta-adrenergic G-protein coupled receptor (GPCR) and only recently has it been confirmed for adenosine A1 and A2a receptors. Only very recently has the binding thermodynamics of ligand-gated ion channel receptors (LGICR) been investigated and data for four receptors have been reported showing that all of them are thermodynamically discriminated. While it seems difficult at present to find a reasonable explanation for the thermodynamic discrimination phenomenon in GPCR, some hypotheses can be suggested for LGICR. Since global delta H degree and delta S degree values of the binding process are expected to be heavily affected by rearrangements occurring in the solvent, thermodynamic discrimination in LGICR is at least logically understandable admitting that the observed delta H degree (and then delta S degree) values are determined by both specific binding and abrupt variation of water-accessible receptor surfaces consequent to the setting up of the channel opening. | lld:pubmed |
| pubmed-article:9658581 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9658581 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9658581 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9658581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9658581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9658581 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9658581 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:9658581 | pubmed:issn | 0014-827X | lld:pubmed |
| pubmed-article:9658581 | pubmed:author | pubmed-author:BoreaP APA | lld:pubmed |
| pubmed-article:9658581 | pubmed:author | pubmed-author:GilliPP | lld:pubmed |
| pubmed-article:9658581 | pubmed:author | pubmed-author:VaraniKK | lld:pubmed |
| pubmed-article:9658581 | pubmed:author | pubmed-author:DalpiazAA | lld:pubmed |
| pubmed-article:9658581 | pubmed:author | pubmed-author:GessiSS | lld:pubmed |
| pubmed-article:9658581 | pubmed:issnType | lld:pubmed | |
| pubmed-article:9658581 | pubmed:volume | 53 | lld:pubmed |
| pubmed-article:9658581 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9658581 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9658581 | pubmed:pagination | 249-54 | lld:pubmed |
| pubmed-article:9658581 | pubmed:dateRevised | 2000-12-18 | lld:pubmed |
| pubmed-article:9658581 | pubmed:meshHeading | pubmed-meshheading:9658581-... | lld:pubmed |
| pubmed-article:9658581 | pubmed:meshHeading | pubmed-meshheading:9658581-... | lld:pubmed |
| pubmed-article:9658581 | pubmed:meshHeading | pubmed-meshheading:9658581-... | lld:pubmed |
| pubmed-article:9658581 | pubmed:meshHeading | pubmed-meshheading:9658581-... | lld:pubmed |
| pubmed-article:9658581 | pubmed:year | 1998 | lld:pubmed |
| pubmed-article:9658581 | pubmed:articleTitle | Receptor binding thermodynamics as a tool for linking drug efficacy and affinity. | lld:pubmed |
| pubmed-article:9658581 | pubmed:affiliation | Dipartimento di Medicina Clinica e Sperimentale, Università di Ferrara, Italy. bpa@dns.unife.it | lld:pubmed |
| pubmed-article:9658581 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:9658581 | lld:pubmed |