Pharmacological receptors

The principle of specific chemical recognition is common to ligand—macromolecule interactions, but this alone does not suffice to define a receptor in the pharmacologic sense. Rather, it is the combination of chemical specificity or recognition and the capacity to initiate biological response or transduction that define the pharmacologic receptor (1,10,11). 

Fig. 3. Information flow at a pharmacologic receptor. The receptor is depicted as having the three components recognition, coupling, and transduction.

Elucidation of the stmctural requirements for dmg interaction at the recognition site is by the study of stmcture—activity relationships (SAR), in which, according to a specific biologic response, the effects of systematic molecular modification of a parent dmg stmcture are determined. Such studies have permitted the classification of discrete classes of pharmacological receptors. For example, the neurotransmitter acetylcholine acts at both peripheral and central receptors which are of at least three distinct types. The effects of acetylcholine are mimicked in smooth and cardiac muscles and secretory... 

The pharmacological receptor of cardiac glycosides is the sarcolemmal Na+/K+-ATPase expressed on most eucaryotic membranes. It was characterised biochemically in 1957 by J. Skou, who was awarded with the Nobel Prize in chemistry in 1997. The sodium... 

De Lean, A., Hancock, A. A. and Lefkowitz, R. J. (1982). Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes, Mol. Pharmacol., 21, 5-16. 

In vitro studies on binding of radiolabeled nicotine to pharmacological receptors in brain tissue... 

Though there are hardly any restrictions to choosing a target, pharmacological receptors are investigated most frequently. The nature of the receptor, v hether it is membrane-bound or soluble, determines which separation technique is used to terminate the binding assay. For the former, filtration or centrifugation are favored as separation steps, while for the latter suitable methods are gel filtration, equilibrium dialysis, precipitation or adsorption of the nonbound marker by charcoal [23, 24]. 

As an alternative to targeting brain tumours which express the TfR, the transferrin approach can be used for the delivery of fusion proteins which bind to pharmacological receptors inside the central nervous system. An example of this is the construct consisting of nerve growth factor (NGF) and transferrin described in Section 11.8.2.3. The transferrin moiety in this type of construct will enable it to enter the brain, upon which the drug moiety will act by binding to its receptor. This approach seems especially suitable for compounds that cannot pass the blood-brain barrier, such as peptides and other hydrophilic substances. 

Kenakin TP. Pharmacological Analysis of Drug-receptor Interaction. New York Lippincott-Raven, 1993. Kenakin TP, Bond RA, and Bonner TI. Definition of pharmacological receptors. Pharmacol Rev 1992 44 351-362. 

IgE-medlated release of mast cell contents. Inset, Intact mast cell with histamine stored In granules. An IgE antibody molecule Is depicted adjacent to the mast cell. Two IgE molecules combine with a mast cell (sensitization). The attachment of an antigen (allergen) to the sensitized mast cell Initiates release of histamine (and other substances) from the mast cell. This degranulation can be prevented by such agents as isoproterenol, theophylline, epinephrine, and cromolyn sodium. H antihistamines do not interfere with degranulation but instead prevent actions of histamine at various pharmacological receptors. 

Interestingly, the lissosphincter subunits (the bladder base) have separate pharmacological receptors from the remainder of the detrusor, but without anatomical or histological boundaries, and integrate in micturition. Lissosphincter muscle bundles proceed into the ceph-alad portion of the prostatic urethra in the male or the... 

The pharmacophore is another example of a species with a distinct level of complexity lying between the systems described as atoms and those described as molecules. The existence of a pharmacophore is an emergent property defined by a pharmacological receptor and this confers upon it the identity of a complex system. 

The site of action may be an enzyme, a pharmacological receptor, another type of macromolecule, or a cell organelle or structure. The interaction of the toxic compounds at the site of action may be reversible or irreversible. The interaction is, however, assumed to initiate a proportional response. If the interaction is reversible, it may be described as follows ... 

The time spent reviewing the pharmacology receptors was just right. ... 

Withdrawal reactions are more problematical. Hypnotics, by and large, are benzodiazepine like in their pharmacology, receptor binding, etc. The main differences relate to duration of action and to putative selectivity of binding. The benzodiazepine withdrawal reaction has been described many times, and rating scales have been developed to measure the symptoms. Withdrawal reactions from hypnotics would be expected to display similar symptomatic patterns and to follow time-courses dictated by the pharmacokinetic properties of the drug. 

Hourani SMO, Cusack NJ. Pharmacological receptors on blood platelets. Pharmacol Rev 1991 43 243-298. 

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