Morphine; How does it work?
Hey Everyone!
I was wandering around checking the latest news and look what I’ve found; according to this article, there could be a biochemical mechanism existing in mammals capable of producing morphine, a strong pain-relieving drug, got from Opium.
I’ve heard a lot about this drug but I never really cared how it works; so I started exploring, and I learned a lot. Now what is Morphine exactly? To answer this question we have break through some essential cell biology and biochemistry.
Since opioids bind to opioid receptors and opioid receptors are a group of G protein coupled-receptors, I’ll start with a brief history about G Proteins.
G proteins (or Guanine nucleotide-binding proteins) are heteromeric (i.e., made of three different subunits) proteins which belong to a larger group of enzymes called GTPases. The subunits are:
- Gα, the binding site. When the complex is activated, the Gα subunit swaps GDP for GTP.
- Gβ
- Gγ
You can consider these proteins some sort of messengers in our cells. They transmit chemical signals outside the cell and cause changes inside the cell. They can transmit several types of signals from hormones, neurotransmitters and other signaling factors. G-protein linked receptors are receptors that pass through the cell membrane. Signal molecules bind to the receptor outside the cell. The receptor inside the cell activates a G protein. The G protein activates a chain of further compounds, and finally causes a change downstream in the cell. Now, when G protein complexes bind to a three phosphate group, forming GTP (Guanosine triphosphate) they turn on; because just like ATP (Adenosine triphosphate) the phosphate groups function as molecular switches. When the G proteins attach to a complex containing only two phosphate groups, forming GDP (Guanosine diphosphate), they turn off.
G Proteins are associated with 1) the inner surface of the plasma membrane
and 2) transmembrane receptors of hormones, etc. these are called G protein coupled-receptors (GPCRs). These transmembrane proteins wind 7 times back and forth through the plasma membrane (check out the figure!). The ligand-binding site of them is exposed outside the surface of the cell and the effector site extends into the cytosol. Some of the ligands are protein and peptide hormones.
Binding of a ligand to the receptor, activates a G protein in the cytosol. This initiates the production of a “secondary messenger” (the primary messenger being the receptor) and triggers a series of chain reactions in the cell, which eventually leads to the production of appropriate genes in response to the signal it had received. Furthermore, they also regulate many immediate effects within the cell which doesn’t include genes at all!
Now, the Opioid receptors are a group of GPSRs with Opioids as their ligands. They are found predominantly in the central nervous system (CNS). As you may know, Opioids are known as pain-relievers due to decreased perception of pain, decreased reaction to pain and also increased pain tolerance.
Back to Morphine, this drug is the prototype Opioid. In medicine, morphine is used to relieve severe agonizing pain or suffering; and as you know, it has a high potential for addiction.
Morphine, no matter how it is administered, makes its way to the CNS. There, morphine interacts with specialized opioid receptors. These receptors, when contacted morphine will cause changes in brain neurons, controlling various behaviors; all of the well-known effects (pain relief, sleepiness, euphoria etc.) are due to the interaction of morphine with brain opioid receptors.
Now, after recent researches, it’s obvious that Opioid receptors and genes are gonna be an exciting new topic of discussion in the world of Biology!
