Mobile receptor model

The mobile receptor model was proposed by Cuatrecasas and by De Haen in an attempt to explain why so many different drugs, hormones, and neurotransmitters can activate adenylate cyclase. According to classical concepts, a recognition site is permanently associated with an effector site, and will regulate its operation on a one-to-one or some other stoichiometric basis. The recognition site is, of course, specific. 

Taking the two receptor model as a le, it may be noted that those activities ch have been shown to require continuous receptor occupancy, such as arachidonate mobilization and the fonnaticm of dx>sphatidic add, are mediated through the high affinity pathway and represent a receptor-hgand mediated mechanism while those receptor activities that require only transient receptor occupancy, such as the synthesis and breakdown of phosphoinositides, correspond to the moderate affinity proteolytic PARI pathway. The feet feat immunoinhibitoty effects at either receptor can be overcome at elevated thrombin levels merely indicates fee relatively high affinities of thrombin binding at both sites ( 0.5nM and lOnM, respectively) as compared with fee relatively low affinities of fee... 

Swillens, S. J.E. Dumont. 1977. The mobile receptor hypothesis in hormone action A general model accounting for desensitization. J. Cyclic Nucleot. Res. 3 1-10. 

Neurokinin-1 Receptor. A homology model of the neurokinin-1 (NKi) receptor was built from the X-ray structure of rhodopsin, using the MOBILE (modeling binding sites including ligand information explicitly) approach. In this procedure, a preliminary model is generated, which is afterwards refined... 

ACT-078573 (20) is the first oral orexin receptor antagonist that penetrates the blood-brain barrier and is capable of inducing a transient and reversible blockade of the two receptors, 0X1 and 0X2 [61]. In animal models, the administration of 20 resulted in a dose-dependent decrease in alertness and increased non-REM and REM sleep. The compound, administered at oral doses ranging from 10 to 300 mg/kg, dose-dependently decreased alertness in rats and exhibited increased duration of REM and non-REM sleep, indicating no intrusive REM sleep that is characteristic of narcolepsy. In dogs, treatment with 20 (10-100 mg/kg p.o.) resulted in dose-dependent reductions in mobility and also induced signs of clinical somnolence. 

Ampakines are drugs that potentiate currents mediated by AMPA-type glutamate receptors. In behavioral tests, ampakines are effective in correcting behaviors in various animal models of schizophrenia and depression. They protect neurons against neurotoxic insults, in part by mobilizing growth factors such as brain-derived neurotrophic factor (BDNF). 

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