The influence of the cellular context on receptor function: a necessary consideration for physiologic interpretations of receptor expression studies

The cell model studied has a fundamental influence on the function and regulation of G protein linked receptors. These cell-dependent effects are illustrated in the current communication focusing on M3 muscarinic, CCK and GRP receptors. Receptors interact with multiple cellular mechanisms. The most obvious are those involved in coupling to signaling mechanisms such as G proteins. Receptors are themselves phosphorylated and dephosphorylated by cellular kinases and phosphatases. Receptors may sequester, internalize, down-regulate and recycle via interactions with a number of separate cellular mechanisms. When the number and complexity of interactions between the cell and the receptor are taken into account it is not surprising that the cell model has a primary influence on receptor function and regulation. The implications of the importance of the cell model in receptor function for studies aimed at answering physiologic questions are discussed.