Morphine… a dragon of bliss or an imposter?
The name morphine has its roots in Greek mythology. Morpheus is the leader of Oneiroi, the dark winged creatures that represent spirits of dreams. He is the one with the amazing ability to appear in dreams of mortals in any form, he manifests himself in dreams of kings to convey the messages to gods.
He was the dream spirit sent by Zeus to visit Agamemnon and urged him to fight In Homer’s Iliad.
As per Ovid’s Metamorphosis he was one of the thousand sons of sleep.
“King Sleep was father of a thousand sons — indeed a tribe — and of them all, the one he chose was Morpheus, who had such skill in miming any human form at will. No other Dream (Oneiro, Morpheus’ brother) can match his artistry in counterfeiting men: their voice, their gait, their face — their moods; and, too, he imitates their dress precisely and the words they use most frequently. But he mimes only men…”
Morpheus implies — the Greek word “morphe” means “form” — he was the one who shapes and forms the dreams.
What an appropriate name for the wonder drug. But sure there is more in common between these great epics and the substance itself, The Iliad and the Odyssey were presumably written under the effects of morphine.
Morphine is an alkaloid extracted from poppy (Papaver somniferum), its cultivation dates back to stone ages. It does its magic by binding to specific receptors on various cells, tissues and organs in the body and provides not only the pain relief but experience that anyone can die for, experience of bliss!!!
What the heck are morphine receptors doing in my body?
Although it was known since mid 60’s that these analgesics bind to specific receptors in the brain, the plot thickened in 1974 when two independent researchers discovered two natural substances in brains of pigs (enkephalins) and calves (endorphins) that bind to receptors called opiate receptors.
These substances were isolated analysed and found to be small proteins, peptides to be precise that could perfectly fit the binding site of the receptor just like a key fits the lock. Here is a nice description (image courtesy Pearson Education Inc) of their structure and how the binding takes place.
The receptors themselves are also protein molecules, made from chains of amino acids held together by binding one’s tail with other’s head as discussed in an earlier post, molecular tweets. These proteins are often coiled and folded in elaborate structures and stick themselves to cell membranes at various sites in the body, as if the mother snake dragons are coiled up and resting in their respective nests, waiting for the baby dragons to arrive and tickle their tails to unleash the power within.
Each and every cell membranes in our body is manifested with millions of these dragon nests where dragons are wagging their tails in the extracellular space, inviting baby dragons to come and tickle.
Baby dragons are also tiny chemicals, an arrangement of specific set of molecules made from amino acids or variations thereof. Each one has a specific sequence that enables it to find the mother dragon and attach to its receptors and tickle the mother dragon to perform its action.
Enkephalins and endorphins are the baby dragons that bind to opiate mother dragon in the nest. There are two types of enkephalins named depending on the last amino acid at the tail, Met- enkephalin is a pentapeptide (Tyr-Gly-Gly-Phe-Met) with methionine at the end and Leu-enkephalin is also a pentapeptide with same sequence (Tyr-Gly-Gly-Phe-Leu) except leucine at the end.
Similarly there are five types of endorphins (endogenous morphine) in the body called α-endorphin (Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr), β-endorphin (Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu), γ-endorphin (Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu) , α-neo-endorphin (Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys), and β-neo-endorphin(Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro).
When it comes to peptides it is the sequence of amino acids that matters. There is a lot in common between different types of endorphins in terms of sequence for example there is one additional amino acid at end of γ-endorphin as compared to α-endorphin, whereas β-endorphin has an extra chain of 15 amino acids at the end.
Similarly α-neo-endorphin and and β-neo-endorphin share first 4 amino acids (Tyr-Gly-Gly-Phe) with α, β and γ endorphins. There is only one amino acid difference between α-neo and β-neo, α-neo-endorphin has Lysine at the end where as β-neo-endorphin has proline.
Morphine is kind of an imposter, it is not a peptide as such but its structure is kind of similar to endorphins, it is still capable of tickling and binding to the mother dragon.
Before we get too high on morphine lets talk about another baby dragon, the baby that acts as its antidote. Naloxone is an antagonist, an antagonist is the chemical that binds to the same receptor, but does the opposite of agonist. That is why when administered to drug overdose patients it quickly bumps off the morphine from its receptor and takes its place and the effect of morphine wears off instantly, as if the dragon has gone silent again once the troublesome baby is shaken off its tail.
Opioids work by their action on various sites in the body, dorsal horn of spinal cord is one such area. The spinal cord dorsal horn is the key region of the central nervous system (CNS) where sensory information is received, integrated, and relayed upstream to the brain. Dorsal horn is well connected to receive its input from various kind of receptors such as nociceptors, chemoreceptors, and thermo receptors that respond to stimuli from the skin, muscles, joints, and viscera. We have briefly covered how pain receptors work in a previous post.
Opioids acts at presynaptic nerve terminal as well as postsynaptic neuron that carry the pain signal to the brain. The presynaptic action is to inhibit release of the neurotransmitter. It acts by either inhibiting entry of calcium ions into nerve cells or enhancing outward movement of potassium ions, or by inhibiting adenylate cyclase (AC) enzyme that converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and eventually facilitates the release of neurotransmitter in the synaptic cleft to pass the pain signal forward.
So this works effectively by regulating the pain transmission switches, when pain regulator is turned few notches down we don’t feel the pain.
Opioids also affects the reward circuitry of the brain that resides in the ventral tegmental area of the brain or VTA in short. VTA is rich in neurons that produce another wonder substance called dopamine.
Dopamine is a monoamine neurotransmitter formed during the synthesis of norepinephrine which is another neurotransmitter that works in sympathetic nervous system to prepare an animal for either “fight or flight” in emergencies.
Dopamine is essential to the normal functioning of the central nervous system. A reduction of dopamine in the brain is associated with the development of Parkinson’s disease.
Dopamine plays a key role in cognition, motivation, orgasm, intense emotions relating to love and of course drug addiction. Neurons in VTA region not only produce dopamine but also ship it to various regions of the brain all the way from brainstem to prefrontal cortex.
VTA is also rich in neurons that produce another key chemical called γ-Aminobutyric acid or GABA. GABA is a key inhibitory neurotransmitter of central nervous system. GABA works by reducing neuronal excitability. Opioids are known to affect GABA neurons by binding to their receptors, binding hyperpolarizes the neurons and reduces the release of GABA which in turns lets the dopamine neurons continue pumping the good stuff in regions of brain that create the euphoria often associated with opioid use and abuse.
No wonder how people get addicted to these substances…we don't just feel bliss, we are rewarded for it.
Now what about body’s internal morphine, endorphins?
Endorphins work the same way as morphine and are body’s internal pain suppressor and ecstasy inducers. Endorphins are internally produced by body, a kind of organic morphine, organic molecules of bliss.
There are many ways to release endorphins in the body, exercise is one such way, the runner’s high feeling is the effect of endorphins. Gossiping, social interactions, laughing, bonding, meditation, showing compassion, eating certain type of food like chocolates, hot peppers etc are all associated with release of endorphins.
Are the endorphins addictive ? I think the evidence points to affirmative answer.
But it is a good kind of addition, it is the addiction to bliss, addiction to life, addiction to molecules of life. It is this addiction that binds us “the descendants of achilians and likes”, the “moving pouches of molecular machinery” to keep moving, keep navigating the seas of life, winning the trojan wars, fooling the enemies with wooden horses or dragons of bliss.
Originally published at scriptgrandeur.wordpress.com on April 5, 2015.