RECEPTORS FOR CELL SIGNALLING

Intercellular signal transduction

Cells in multicellular organisms need to be able to communicate with each other in order to respond to external stimuli and to coordinate their activities to achieve homeostasis. Such communication is termed intercellular signalling and is achieved by:

• The release by the ‘signalling’ cells of signalling molecules, referred to as endogenous agonists or first messengers.

• The specific recognition and binding of these agonists by receptor molecules, simply referred to as receptors, located either in the cell membrane or in the cytoplasm of the ‘target’ cell. Each cell membrane contains between 103 and 106 molecules of a given receptor. Binding of the agonist to a specific binding domain on the receptor changes the receptor from its inactive, resting state, to an active state. Exceptionally, a receptor may possess activity in the absence of agonist. Such receptors are said to possess constitutive activity.

• The initiation of a sequence of molecular events commonly involving interaction between the active receptor and other, so-called effector molecules, the whole process being referred to as intracellular signal transduction which terminates in the final cellular response.

Agonist signalling molecules range from the gas nitric oxide, amines, amino acids, nucleosides, nucleotides and lipids to hormones, growth factors, interleukins, interferons and cytokines. These molecules are either lipophilic or hydrophilic. Lipophilic signalling molecules such as the steroid hormones (progesterone, oestrogen and testosterone) and non-steroid hormones (thyroxine and triiodothyronine) can readily cross the cell membrane, in which case they bind to receptors located in the cytoplasm.