TERMINATION OF EFFECTOR RESPONSES TO AGONISTS - ANALYSIS OF AGONIST DISPOSITION MECHANISMS

Termination of action, as the term is often used by physiologists and pharmacologists, describes a restorative process in an effector system. Traditionally, the term is invoked when dealing with the action of nerve-released or exogenously added transmitter substances and their analogues. The cells of a tissue or organ responding to an agonist, in a state of altered activity due to receptor activation, are released from agonist control as the number of inciting molecules diminishes. Response termination, as the term is used here, is concerned strictly with the reduction in the number of active agonist molecules at the locus of action, the processes which enforce this dilution, and its consequences on magnitude and duration of response. There are no established biochemical procedures or criteria which discriminate between processes terminating action, by removal of that critical concentration of agonist at the receptors. Inhibition of even a major metabolic process for agonist reduction may have an inconsequentila effect on termination of action. What is important in termination of action is not that a particular process inactivates 20 or 80% of a particular agonist in the total responding system, but how significantly it influences the concentration and duration of that agonist at the receptors. Topics discussed include identification of terminating mechanisms, diffusion as a mechanism of agonist dilution and response potentiation and termination.