Agonist concentration gradients as a generalizable regulatory implementation strategy.
This article proposes a general mechanism by which biphasic dose-response relationships occur in pharmacological and toxicological experimental systems. Such biphasic responses are mediated via a strategy of differential binding to stimulatory and inhibitory receptor subtypes based on agonist concentrations. Such a strategy is widely seen in pharmacological systems and has been demonstrated in toxicological-related biphasic dose responses in which the treatment altered levels of endogenous agonists.
Calabrese
E J
EJ
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst 01003, USA. edwardc@schoolph.umass.edu
Baldwin
L A
LA
D000222:Adaptation, Physiological; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D006801:Humans; D008962:Models, Theoretical; D010600:Pharmacology; D015398:Signal Transduction; D018675:Toxicity Tests