Multiple varied receptors

Multiple Varied Receptors Within a Single Coordination Compound... 

Figure 10. Multiple-varied receptors face-to-face porphyrin/crown ether.

Figure 11. Multiple-varied receptors porphyrin/cyclodextrin (Reproduced with permission from reference 63. Copyright 1985, John Wiley Sons, Inc.).

Figure 12. Multiple-varied receptors macrobicycle with sites for metal ion and substrate (Reproduced from reference 65. Copyright 1990, American Chemical Society).

Figure 13. Multiple-varied receptors-macrobicyclic cyclidene with sites for metal ion and substrate top, sketch of ternary complex right, side view of substrate complex left, view into cavity that contains substrate. (Reproduced with permission from reference 69. Copyright 1989, Kluwer).

The opioid peptides vary in their binding affinities for the multiple opioid receptor types. Leu- and Met-enkephalin have a higher affinity for 5-receptors than for the other opioid receptor types (68), whereas the dynorphin peptides have a higher affinity for K-sites (69). P-Endorphin binds with equal affinity to both p- and 5-receptors, but binds with lower affinity to K-sites (70). The existence of a P-endorphin-selective receptor, the S-receptor, has been postulated whether this site is actually a separate P-endorphin-selective receptor or is a subtype of a classical opioid receptor is a matter of controversy (71,72). The existence of opioid receptor subtypes in general is quite controversial although there is some evidence for subtypes of p- (73), 5-(74), and K-receptors (72,75), confirmation of which may be obtained by future molecular cloning studies. 

These results further support the hypothesis that potent synthetic agonists of octopamine-sensitive adenylate cyclase should be useful as selective pesticides. The results also suggest that if compounds could be developed which were potent against the octopamine-sensitive adenylate cyclases present in a wide variety of insect species, they should, similarly, have a wide spectrum of insecticidal activity. However, in order to develop such compounds, much more needs to be known about a) the molecular pharmacology of octopamine receptors and b) the interspecies differences which seem to exist in the characteristics of such receptors. In other words, we need to know if there exist single or multiple octopamine receptor subtypes which interact with adenylate cyclase, and if multiple, how these subtypes vary among different species. 

Fig, 2. Regulation of L-type channels by multiple second messenger systems. The cartoon is based on what is known or speculated about how L-type Ca channels might be regulated by proeesses that involve phosphorylation by different receptor mediated pathways. The actual receptors and number of pathways may vary in different cell types. The cartoon is loosely based on events that might occur in a cardiac cell. 

Receptor plasticity could be invoked as the underlying common trait of multiple receptors. For example, although the multiple adrenergic isoreceptors are similar, they react to the common neurotransmitter norepinephrine (2.4) in a quantitatively different manner. They also show a drug specificity that varies from organ to organ and differs in various species of animals. In subsequent chapters of this book, receptor multiplicity as the rule rather than the exception will become amply evident. It is to be hoped that, in time, the comparison of isoreceptor molecular structures will provide precise criteria for their differentiation. 

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