Specific receptor theory

FIGURE 11-2 Schematic illustration of two possible ways general anesthetics may act on the nerve membrane. In the general perturbation theory, anesthetic molecules lodge in the lipid bilayer and inhibit sodium channel function by disrupting membrane structure. In the specific receptor theory, anesthetics inhibit the opening of the sodium channel by binding directly to the channel protein. 

Olfactory receptors have been a subject of great interest (9). Much that has been postulated was done by analogy to the sense of sight in which there are a limited number of receptor types and, as a consequence, only three primary colors. Thus attempts have been made to recognize primary odors that can combine to produce all of the odors that can be perceived. Evidence for this includes rough correlations of odors with chemical stmctural types and the existence in some individuals having specific anosmias. Cross-adaptation studies, in which exposure to one odorant temporarily reduces the perception of a chemically related one, also fit into this hypothetical framework. Implicit in this theory is the idea that there is a small number of well-defined odor receptors, so that eventually the shape and charge distribution of a specific receptor can be learned and the kinds of molecular stmctures for a specified odor can be deduced. 

By utilizing complete dose-response curves, the method devised by Barlow, Scott, and Stephenson [9] can be used to measure the affinity of a partial agonist. Using null procedures, the effects of stimulus-response mechanisms are neutralized and receptor-specific effects of agonists are isolated. This method, based on classical or operational receptor theory, depends on the concept of equiactive concentrations of drug. Under these circumstances, receptor stimuli can be equated since it is assumed that equal responses emanate from equal stimuli in any given system. An example of this procedure is given in Section 12.2.1. 

The primary need of receptor modeling today is a general theory within which to operate. Each specific receptor model application should be derivable from this framework. If not, either the application of the theory is incorrect, or the theory must be changed. Throanorton and Axetell have compiled the applications. Henry J and Watson 2) have outlined the theory including some of those applications. The theory must be expanded to include them all. 

Other antidepressant drugs are listed in Table 10.4. Their principal pharmacological actions include inhibition of re-uptake of NA, 5-HT, or both, and they generally have some additional direct effects on specific receptors, which in theory should assist their therapeutic action. 

Hence, it is believed that general anesthetics exert most, if not all, of their effects by binding to one or more neuronal receptors in the CNS. This idea is a departure from the general perturbation theory described earlier that is, that the inhaled anesthetics affected the lipid bilayer rather than a specific protein. Continued research will continue to clarify the mechanism of these drugs, and future studies may lead to more agents that produce selective anesthetic effects by acting at specific receptor sites in the brain and spinal cord. 

Theories abound, which relate those two vocabularies, but no one of them has emerged as predominant. Many of the theories suppose the existence of specific receptor sites on the surface of the receptor neurons. One hypothesis posits a set of odors of specific objects (e.g., camphor, sperm, urine, fish) that correspond to pure compounds and represent fundamental submodalities (Beets, 1982). Another (based on molecular biology) proposes dozens—perhaps hundreds—of different types of cell surface receptor proteins, each of which is tuned to a specific odorant compound or class of compounds (Buck, 1996 Zhao et al., 1998). 

According to stereochemical theory, the mechanism of smell depends on the binding of an odor molecule to a specific receptor site, which resembles the lock-and-key mechanism of enzyme catalysis. If two substances fit the same receptor, they should have the same odor, even if they differ in chemical composition. There are seven different kinds of olfactory receptors, each of which will accept a molecule that has the appropriate geometry. For putrid molecules such as hydrogen sulfide (H2S), however, polarity is more important than shape in linking up with a receptor. In addition, if different portions of a molecule fit different receptors, the molecule should have a mixed odor. For example, portions of benzaldehyde fit the camphor-like, floral, and peppermint receptors we recognize the resulting aroma as almond. 

As the existence of specific receptors is as crucial to the theory as the variation in metabolite content, this section examines some classes of receptor families and their variability. Studies of their evolution (Chapter 5 and Appendix 10) demonstrate their ancient roots and their transformation in time into more and more sophisticated structures. Following the differentiations of receptors the secondary metabolites have experienced a concomitant evolution (Appendix 10). 

In 1911 Winterstein (12) proposed his reaction theory of ventilatory control. This theory, which has progressively evolved over the years with the accumulation of new experimental findings and interpretations (13, 14), is based upon the idea that it is the hydrogen ion concentration [H+] in or near specific receptor cells which is the principal stimulus of respiration. Increased ventilation with increases in pco2 is explained on the basis that C02 has acid-forming properties in water—i.e.,... 

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