|MadSci Network: Neuroscience|
Hi, Your question is complicated so we'll break it down into sections. First, as you know glucocorticoids are steroids and steroid receptors are found inside the cell (in the cytoplasm or the nucleus). Thus, to have their effects, steroids have to get into their target cells by crossing the plasma membrane, something they can do quite easily because they are quite hydrophobic (being structurally based on cholesterol). Catecholamines like epinephrine or norepinephrine behave in exactly the opposite fashion. Their receptors are located in the cell membrane because unlike the steroids, catecholamines are hydrophilic and cannot cross the membrane by themselves. Now, when epinephrine (or norepinephrine) binds it's cell surface receptor it causes changes in the conformation of the receptor protein which initiates a signalling cascade inside the cell. Thus, epinephrine or norepinephrine do not have to cross the membrane and exert their effects from outside the cell. Your question about whether they get into neurons brings up some other issues for you to think about though. Remember that whether epinephrine is released as a hormone by the adrenal gland or by a neuron as a neurotransmitter it acts on the same target cells in the brain or other tissues. In the case of a neuron though, it is made by the a cell adjacent to the target (whereas when released by the adrenal gland it has to travel through the blood to distantly located targets) and released into the specialized space between two neurons called the synapse. Not only does the catecholamine go across the synapse and bind to receptors on the postsynaptic cell, but in order to limit the response and to conserve released epinephrine or norepinephrine it is also taken up by the presynaptic cell which originally released it. Thus, by definition it can get into neurons. One last thing for you to consider is what happens on the postsynaptic side. In a case where the frequency of signalling between two neurons is low, what shuts off signalling on the postsynpatic side is just unbinding of the transmitter from its receptor. However, in the cases where the signalling frequency is high, there is usually sufficient transmitter to remain bound to the receptor. You would intuitively think that signalling strength (i.e. the response to the transmitter) would be constant during a sustained stimulus. This is not usually the case. What happens is a sequential process where the receptor becomes desensitized (that is, despite the continual presence of a stimulus of the same intensity the response diminishes). Initially, this involves, changes in the receptor only. If the stimulus remains the receptors (with the transmitter still bound) actually become internalized (i.e. removed from the cell surface) by a process involving a number of other proteins and thus this represents another way for the transmitter to get inside the cell.So, to summarize most of the business of these catecholamine receptors occurs at the cell surface with the catecholamine remaining outside but under certain conditions the hormone can actually get into the target cell. Up until a few years ago, we believed that no signalling occurred once the receptor was internalized. Now however, we know that this had been a gross oversimplification as internalization in addition to being part of the desensitization process may also be critical to activation of other intracellular signalling pathways. Even more amazing is the recent notion that some of these receptors may actually be found in the nucleus thus the neurotransmitter must get inside the cell to activate them. Hope this helps... Terry
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