Receptor action

Florio, V. A., and Stemweis, P. C. (1989). Mechanism of muscarinic receptor action on G0 in reconstituted phospholipid vesicles. J. Biol. Chem. 264 3909-3915. 

The binding and activation steps of receptor action have been dissected computationally, although not yet in a global fashion. The conformational dynamics of the activation of the A3AR have been approximated with respect to isolated portions of the receptor. 

Hall JM, McDonnell DP (2005) Coregulators in nuclear estrogen receptor action. From concept to therapeutic targeting. Mol Interv 5 343-57. 

The release (calcium-dependent) and receptor actions of peptides resemble those of the classical transmitters, the receptors being seven transmembrane-spanning receptors... 

A] and response is here being described rather than explained in terms of a model of receptor action. This is an important difference. 

Finally, we return to models of receptor action and to a further limitation of the early attempts to account for the shapes of concentration-response curves. As already noted, the simple concepts expressed in Eqs. (1.3) and (1.4) do not distinguish between the occupation and the activation of a receptor by an agonist. This distinction, it is now appreciated, is crucial to the understanding of the action of agonists and partial agonists. Indeed all contemporary accounts of receptor activation take as their starting point a mechanism of the following kind ... 

This will be described as the del Castillo-Katz scheme, as it was first applied to receptor action by J. del Castillo and B. Katz (University College London) in 1957 (see also Section 1.4.3). 

The term state rather than condition is often used in this context. However, the latter seems preferable in an introductory account. This is because the del Castillo-Katz mechanism is often described as a two-state model of receptor action, meaning here that the occupied receptor exists in two distinct (albeit interconvertible) forms, AR and AR, whereas three conditions of the receptor (R, AR, and AR ) have to be identified when applying the law of mass action to the binding of the ligand, A. 

Experimental Evidence for G-Protein Coupling in Receptor Action.218... 

EXPERIMENTAL EVIDENCE FOR G-PROTEIN COUPLING IN RECEPTOR ACTION... 

The means used to prepare these agents can be illustrated by the following examples. Practolol (109) gives less clinical bronchoconstriction in some patients than propranolol because its receptor action is more selective. Serious occasional toxicity not related to p-blockade has led to its withdrawal from clinical use. A synthesis is available which relates the absolute configuration of the more potent... 

For the analysis of the primary bluelight receptor action, it is necessary to uncouple the sensory transduction process from the subsequent phototropic reaction... 

Wonerow, R, Neumann, S., Gudermann, T., and Paschke, R. 2001. Thyrotropin receptor mutations as a tool to understand thyrotropin receptor action. Journal of Molecular Medicine 79(12), 707-721. 

Adrenaline, which turns on both receptors, increases heart rate via the beta-1 receptor and dilates airways by the beta-2 receptors. Propranolol, which is a nonspecihc blocker of both beta-1 and beta-2 receptors, decreases heart rate and lowers blood pressure, beta-1 receptor action, but can constrict airways in the lung, beta-2 receptor action, and that is not so good. 

In the 1980s, decades of research began to bear fruit. Pharmaceutical companies were able to design molecules with specific receptor interactions in mind. The driving force behind this effort was the recognition that many of the receptor actions of the TCAs were not helpful and only created unwanted side effects. By designing compounds that did not have so many actions, side effects could be reduced. 

This can be hard to explain. Potential causes include a worsening of the depression, the development of tolerance to the medication s effect, or the loss of placebo effect. Some believe that in our efforts to find safer and more tolerable medications, we have produced a new generation of antidepressants that are not as effective when used long-term. This harkens back to the rich pharmacology versus dirty drug debate. Could the older medications with their multiple receptor actions work better long-term We really don t know. 

In summary, research on steroid receptor action will provide many opportunities to further improve treatment of hormone-dependent cancers. 

Because of multiple receptor actions, which occur at different concentrations, different neuroleptics have different action profiles. There are many classifications for neuroleptic drugs, the least useful of which is probably based on their chemical structure. Other classifications include linear classifications based on the propensity to cause EPS, or multidimensional ones such as the Liege star which combines information on three positive effects (anti-autistic, antiproductive, antipsychotic), and three negative (hypotensive, extrapyramidal, sedative). In a general way, the more sedative neuroleptics such as levomepromazine, used more to treat acute agitation states, cause more hypotension related to alpha blockade, whereas those that act best on delirium (productive states) such as haloperidol tend to cause more EPS. 

RECEPTOR ACTION MECHANISMS IN RECEPTOR SIGNAL TRANSDUCTION... 

These drugs have complex pharmacology but they share a greater ability to alter 5-HT2A-receptor activity than to interfere with D2-receptor action. In most cases, this is accomplished through a partial agonist mechanism. 

Care should be taken not to administer any partial agonist or drug with mixed opioid receptor actions to patients receiving pure agonist drugs because of the unpredictability of both drugs effects reduction of analgesia or precipitation of an explosive abstinence syndrome may result. 

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