Enkephalin is an endogenous opiate. They behave in a similar way
to opium in that they have an analgesic effect thus the similar name.
There are opiate receptors throughout the body, in the brain and peripheral
tissues. Enkephalin is categorized as an endorphin (endogenous morphine).
Some of the different types of endorphins include:
Although it is a short peptide (five amino acids) there are numerous functions:
There are three receptor sites that interact with endorphin peptides
and all three influence each other->allowing for higher complexity, more
options for neural signals.
Patterns of distribution and quantity of receptor sites vary between species and anatomical regions.
1) mu-receptor: sensitive to morphine and similar drugs.
Beta-endorphin also interacts here slightly although it prefers the delta-receptor.
The mu-receptor is thought to deal primarily with analgesia.
There are two subtypes
a)one deals primarily with the analgesic effects
b)another deals with inhibition of breathing->principal reason of death by overdose on heroin and morphine.
2) kappa-receptor: dynorphin interacts here. Stimulation at the kappa-receptor site antagonizes the effect of mu-receptor-mediated analgesia. Calcium channels of the neuron are indirectly affected here and at the delta-receptor site.
|mu stimulation produces euphoria||kappa stimulation results in dysphoria and aversion|
|mu deals with rewarding, increases dopamine release||kappa blocks morphine-induced rewarding, lowers dopamine.|
The presence of endorphins/enkephalins insured that survival comes first,
Areas of the brain that release endorphins are primitive suggesting an early beginning, estimated at 200 mya.
c)entry at spinothalamic pathway
Role of endorphins in humans now-> no longer linked to a hostile environment, now focused on social behaviors and relationships.
A neurotransmitter is released from the presynaptic neuron, aided by Ca++ transport. Receptor sites on the dendrite of the recieving neuron match the molecular structure of the neurotransmitter allowing a fit. Successful binding changes the membrane which either excites or inhibits the post-synaptic neuron.
Opioid receptors are coupled with K+ conductors. Na + and K+ are held on opposite sides of the neural membrane of the post-synaptic neuron, with the inside being slightly more negative than the outside creating an action potential. When enkephalin binds to the delta receptor, the permeability of the membrane is increased for K+ only, it leaks out-->increasing the action potential of the synapse. Normally when the neuron accepts a transmission Na+ flows into the cell creating a slightly positive charge. This charge change lasts about a tenth of a second as Na+ starts flowing back out to create the action potential again. The signal proceeds to travel down the neuron in the same fashion until it reaches the next synaptic cleft where it either excites or inhibits the next neuron. When K+ leaks out due to enkephalin binding the charge difference increases as the inside of the cell body becomes more negative. The action potential is decreased as it takes greater energy for the neuron to reach the firing threshold.
1) Current causes the presynaptic neuron to become Calcium++ permeable
from extracellular fluid.
2) C++ causes exocytosis of synaptic vesicles (contain neurotransmitters).
3) A neurotransmitter travels the synaptic cleft->binds to a complementary receptor.
4) The result is either:
a)EPSP (excitatory post synaptic potential) ->depolarization
b)IPSP (inhibitory post synaptic potential)->hyperpolarization (i.e. making the membrane permeable to K+).
Both IPSP and EPSP can occur together as many neurotransmitters act on the neuron at once-->integration of the signal.
Two neurotransmitters that are thought to transmit nociceptive information are somatostatin and substance P (SP). The latter will be discussed here.
Release of substance P can be inhibited by enkephalin through presynaptic inhibition.
a) Hetero-trimer and inactivated receptor
b) Agonist binding at the receptor causes conformational change-->the G-protein binds.
c) The beta-gamma dimer dissociates
d) The activated GTP-alpha complex then travels to the effector enzyme which makes the membrane K+ soluble.
e) The cycle can be repeated for as long as the agonist binds to the receptor.
(-)mice exhibited some similar characteristics with (+)mice and some not:
Hot-plate assay was used to measure pain responses by supraspinal mechanisms. (-)mice immediately shook their foot when put on the plate while (+) explored the area, then shook their foot (analgesia was greater). (-)mice showed a jump-latency as almost half that of the (+)mice (see graph b)-->supraspinal threshold of pain of (-)mice is lower than that of (+)mice.
A swim test was conducted to examine the effects of stress on analgesia related to enkephalins. The mice swam in a 4 degree celsius water for 90 seconds. The degree of analgesia was the same in (-) and (+) mice. Therefore this test seems to suggest that enkephalins aren't involved in stress-induced analgesia, contrary to previous research. The conclusion of this test might not be wholly accurate since a presumption is being made that swimming in cold water accurately represents a stressful environment.
(-)mice were less inquisitive about a new environment than (+)mice. They tended to stay near a wall, didn't enter the open field much. Less inquisitive, curious-->perhaps lower intelligence.
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