MadSci Network: Neuroscience

Re: Does ADRENAL epinephrine and/or norepinephrine enter the brain..

Date: Sun Apr 30 18:10:13 2000
Posted By: Terry Hebert, Faculty, Universite de Montreal, Biochemistry, Montréal Heart Institute
Area of science: Neuroscience
ID: 956790755.Ns

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 


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