The interaction of drugs with the sarcoplasmic reticulum.

Efforts to determine the mechanisms by which drugs interact with membranes can be facilitated by studies of the SR, which has a relatively simple structure. The fact that the SR lacks most of the specific receptors found on other membranes, notably the sarcolemma, is an advantage, as well as a limitation, in that "nonspecific" drug effects can be evaluated readily in the SR. The presence in the SR of a well-characterized calcium pump protein allows the effects of a given drug on membrane function to be analyzed, and drug effects on the functional properties of the SR can now be correlated with their probable sites of action within the membrane. Equally important is the ability to acquire information regarding the relation between the structure of an amphiphilic drug and its mechanism of interaction with the SR membrane, because these interactions depend on the structural properties of both the membrane and the added agent. The potential sites of interaction of amphiphiles schematically portrayed in Figure 3 may be relevant to membranes other than the SR, as the overall structural properties of this membrane appear not to be unique. For this reason, the interaction of drugs with the sarcoplasmic reticulum membrane may provide structural models that are applicable to other biological membranes.