4 - How drugs act: cellular aspects – excitation, contraction and secretion

Abstract

The link between a drug interacting with a molecular target and its effect at the pathophysiological level, such as a change in blood glucose concentration or the shrinkage of a tumour, involves events at the cellular level. Whatever their specialised physiological function, cells generally share much the same repertoire of signalling mechanisms. In this chapter, we describe excitation, contraction and secretion signalling mechanisms that operate mainly over a short timescale (milliseconds to hours), which account for many physiological responses. The short-term regulation of cell function depends mainly on the following components and mechanisms, which regulate, or are regulated by, the free concentration of Ca2+ in the cytosol, [Ca2+]i: (1) ion channels and transporters in the plasma membrane, (2) the storage and release of Ca2+ by intracellular organelles, (3) Ca2+-dependent regulation of a variety of functional proteins, including enzymes, contractile proteins and vesicle proteins. Because [Ca2+]i plays such a key role in cell function, a wide variety of drug effects result from interference with one or more of these mechanisms. Knowledge of the molecular and cellular details is extensive, and here we focus on the aspects that help to explain drug effects.