Changes in tissue sensitivity to drugs in relation with alteration in receptors by treatment of drugs.

Abstract

Tissues responses for drugs are often altered by chronic administration of drugs and this alteration is one kind of functional abnormality of the tissues. One mechanism under this functional abnormalities is considered to be in changes in receptors for drugs. In this study, we examined amounts and properties of receptors in sub- and supersensitive states caused by pre-exposure of tissues to drugs and the results obtained were summarized as follows. Long term exposure of tissue to agonists or to conditions which elevate concentration of agonist around the receptor caused reduction in amount of receptor without change in its property. Short term exposure to agonists altered the configuration of the receptor accompanying reduction in sensitivity of the tissue to drugs. But amount of receptor in the tissue was not changed. Heterologous desensitization was observed in some cases by exposure to drugs and no significant change was observed in the receptor of the tissue, qualitatively and quantitatively, indicating dysfunction in the process(es) after activation of the receptor. Denervation and chronic treatments with antagonist and ganglion blocker caused supersensitive state accompanying increase in amount of receptor. But in some cases, qualitative change of receptor, increase in affinity of receptor for agonist, seemed to relate with supersensitive state of tissues.