Receptor critical points

Moreover, duration of central NKi receptor blockade is a critical point, as anesthetic-like nerve block caused by non-specific effects on ion channels in peripheral tissues could mask the selective antinociceptive effects of blocking NKi receptors in the spinal cord. The long-acting NKi antagonist L-733,060 maintained blockade of central NKi receptors at a time when peak plasma drug levels had subsided. Therefore, in paw licking experiments, the inhibitory effect of L-733,060 appeared to be due to central NKi receptor blockade (Rupniak et al., 1996). 

Structure-activity relationships of A -THC analogs have revealed three critical points of attachment to a receptor (1) a free phenolic hydroxyl group (2) an appropriate substituent at the C9 position and (3) a lipophilic side chain (Howlett et al. 1988). However, compounds with a dimethylheptyl side chain retain affinity for both CBi and CB2 receptors even when they lack a phenolic hydroxyl (Gareau et al. 1996 Huffman et al. 1996). Moreover, these ligands are CB2-selective (Huffman et al. 1996,1999). 

The use of models based on experimental observations has shown how the regulatory properties at the level of enzymes and receptors can give rise to nonequilibrium, temporal self-organization in the form of sustained oscillations of the limit cycle type. In this, sustained oscillations represent examples of the dissipative structures described by Prigogine (1969). Like spatial or spatiotemporal dissipative structures, limit cycle oscillations occur beyond a critical point of instability and... 

The critical point for all of these sensors is the specificity for the target species, with different oxidizing agents, e.g. ozone, O3, leading to similar changes. The specificity is also a critical issue for biosensors but here the lock and key principle of certain receptors, such as the biotin streptavidin system, can be exploited (78). 

Critical residues were identified through heterologous competition, or affinity of the radiolabeled antagonist to the point-mutated receptor. 

Critical loads and levels are measurable quantitative estimates showing the degree of tolerable exposure of receptors to one or more pollutants. According to present knowledge, when this exposure remains below the critical load and level thresholds, significant harmful effects on specified receptors do not occur (Gregor, 2003). They serve as reference points against which pollution levels can be compared and potential risks to environmental components can be estimated. 

---