Signal recognition by receptors

Author(s): Lohse, M. J.

Journal/Book: Proc GIRI. 1991; 5: 10.

Abstract: Signals both from outside the body -such as light and olfactori stimuli- and from within the body -such as hormones and neurotransmitters- are perceived with the aid of specific receptors. These receptors are proteins which bind the stimulus and then transmit a signal to the intracellular space. The intracellular signals lead via different cascades to alterations of cell and organ function. Four large families of receptors can be distinguished. Three of these are membrane - bound: the G-protein coupled recep- tors (prototypes are the light "receptors" or opsins and the adrenergic receptors), the ion-channel receptors ( such as the GABA-receptors) and the tyrosine kinase receptors (for examole the insulin receptor). The fourth family is composed of intracellular, DNA- binding receptors such as the steroid receptors. Using the G-protein coupled receptors as model systems the principles of receptor function and regulation will be outlined. Receptors display widely varying sensitivities to their stimuli: some -for example rhodopsin- are exquisitely sensitive, whereas others -for example the adrenergic receptors- require hormone concentrations in the micromolar range to become fully activated. Since many hormones and many drugs act at multiple receptor subtypes of differing sensitivities, complexe dose-response relationships may exist. Thus, a hor- mone may produce -at different concentrations- entirely different and sometimes even opposite responses. Adrenaline, for example. can cause stimulation of cAMP-produc- tion via 8-receptors. inhibition of cAMP-production via a2-receptors, and stimulation of phosphoinositol-metabolism via a1-receptors. In recent years considerable evidence has accumulated to show that cells are not just passive receivers of receptor- mediated signals, but that they modulate their res- ponses by interfering with the signal transmission machinery. Many of these modulatory events have the characteristics of feed- back loops in which a signal modulates its own response. In the model system of the 8- adrenergic receptor/Gs/adenylyl cyclase, sti- mulation of the receptor by its agonists results in short-term modulation of receptor responsiveness and long-term modulation of receptor expression. e proteins. Modulation of receptor expression is achieved by enhanced transcription -via cAMP- and glucocorticoid-responsive elements- reduced stability of the receptor mRNA, and agonist-induced degradation of the receptor protein. ill help in the understanding of drug action and in the development of new therapeutic principles.

Keyword(s): hom. rel. biochem. receptor

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