Receptors inactivation theory

Receptor inactivation theory, initially proposed by Gosselin in 1977 has been widely disseminated by Kenakin (35)and to some degree is based on the two-state model originally proposed by Katz and Thesleff (41) for ion channels, specifically the Torpedo nicotinic receptor. where the multimeric receptor exists in active and inactive states, with ligand binding altering the equilibrium between these two states. Receptor inactivation theory reflects a synthesis of both occupancy and rate theories providing an alternative consideration for the study of the RL interaction. 

Inactivation theory assumes that the RL complex is an intermediate "active" state that gives rise to an inactive form of the receptor, R, which is part of an RL complex termed RL. The rate term, is the rate of association and is the rate of dissociation of the RL complex (Equation 10.5). is the rate constant for the transition from RL to RL with the rate constant for the regeneration of the active form of the receptor, R being k,. The response is proportional to the rate of R formation which is equal to (R L), a variable that is dependent on the number of receptors occupied and the rate of R formation. Unequivocal experimental data to support reeep-tor inactivation theory has been difficult to obtain as has data to distinguish between occupancy, rate and inactivation theories of the RL interaction. Nonetheless, the inclusion cf an additional step in terms of the active recep-... 

In terms of classical receptor theory, equiactive responses to an agonist are compared in the control situation ([A]) and after irreversible inactivation of a fraction of the receptors ([A7]). Assume that after alkylation the remaining receptors equal a fraction q ... 

Exactly how local anesthetics inhibit the sodium channel from opening has been the subject of much debate. Although several theories exist, the current consensus is that local anesthetics temporarily attach to a binding site or receptor located on or within the sodium channel.16,36,60 These receptors probably control the opening of the channel, and when bound by the anesthetic molecule, the sodium channel is maintained in a closed, inactivated position. Several sites have been proposed to explain exactly where the local... 

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