We found that this isoform is specifically required for relaying morphine-induced itch. Very interestingly and unexpectedly, we found that this isoform is not involved in morphine analgesia.
So this, actually, is the first evidence to show that a morphine isoform has nothing to do with morphine analgesia. And we believe MOR1D is the only isoform involved in morphine-induced itch.
There are so many other isoforms, and some of the isoforms we know, they are also expressed in the spinal cord. However, there are many downsides to utilizing such potent medications — even though they are generally effective. The most widely recognized downside is the habit-forming nature of these medications. Even when taken exactly as prescribed, medications like hydrocodone and oxycodone can result in physical and psychological dependence in a relatively short period.
Aside from the risk of addiction, it is estimated that close to 80 percent of all individuals who are using an opiate narcotic medication experience at least one side effect during their treatment course. Some additional physical side effects include:. These are not the side effects associated with opiate abuse — these are side effects that any individual who is prescribed an opiate painkiller is liable to experience.
In addition to these physical side effects, many behavioral and psychological side effects can occur.
However, the physical side effects are generally more prevalent when the medication is taken as prescribed by a medical professional. Out of all physical side effects, one of the most disruptive is excessively itchy skin.
What is in opiates that makes the skin itch severely, and what can be done to prevent this side effect from occurring? New data that was published in the Natural Chemical Biology journal suggests that some opioids can trigger an immune system response that affects one of the major receptor proteins on mast cell surfaces. New findings published in the journal Nature Chemical Biology by UNC School of Medicine scientists show that MRGRPX2, a receptor protein on the surface of mast cells, can trigger the immune system response that leads to itching associated with some opioids.
This response is also important for things like allergies. And this is what presents itself as itching. We think that our data could potentially explain why degranulation occurs as a side effect of opioid ligands morphine and other drugs , something that is well-known but not well-understood.
The findings are significant not only because they offer a potential explanation for opioid-induced itching, but also because the data suggest a way to characterize the function of the orphan receptor MRGRPX2. Currently there are about orphan receptors in humans. They are "orphan" because, though we know they exist, we don't yet know what they do.
The Roth lab screens these receptors against thousands of small molecules to find out what might activate them. This process involves a combination of physical screening and computational modeling. Once that tentative picture was in place, we were able to use computational tools to create a more precise model of the site. The computer modeling, performed by co-first author Joel Karpiak, a graduate student at the University California at San Francisco, tested 3.
The physical data combined with the computational models allowed the researchers to create a chemical probe designed to interact specifically with MRGRPX2. This new tool made it possible to gain a more precise understanding of this receptor's effects without the noise of other receptors.
An opioid might activate the orphan receptor, but it might also activate other receptors that it interacts with.
0コメント