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Endomorphins

Endomorphins are

Endomorphins belong to the

Both endomorphins-1 and 2 are tetrapeptides, meaning they both consist of four amino acids. Endomorphin-1 has the primary structure of Tyr-Pro-Trp-Phe, while Endomorphin-2 has the primary structure of Tyr-Pro-Phe-Phe. The endomorphins must not be confused with the peptides structures of enkephalins, endorphins, and dynorphins, which are comprised of the amino acid sequence, H-Tyr-Gly-Gly-Phe.^[2]

Function

Endomorphins are complex opioid neurotransmitters which have a variety of functions. Complex opioid systems control physiological processes which includes pain, reward, stress, immune responses,

Most of the opioid peptides undergo enzymatic degradation. Degradation prohibits competitive inhibition of μ-opioid receptors. This reduces competition for the receptor binding sites, facilitating biological activity. Endomorphins are vulnerable to enzymatic cleavage which results in endomorphin degradation. The protein, DPP IV catalyzes endomorphin degradation.^[7]

Neurophysical role

There are multiple areas where μ-opioid receptors and endomorphins dictate biological processes. Such processes include pain, stress, and complex functions including autonomic, cognitive, neuroendocrine, and limbic homeostasis. Endomorphins control the nociceptive pathways. There is a transmission of nociceptive information that is a direct input from primary afferents neurons. Endomorphin-2 is more heavily involved in the early stages of nociceptive information processing, which serves a regulatory function that hyperpolarizes the membranes of the neurons on the dorsal horn and decreases the postsynaptic response. The development of tolerance limits the use of opioid as pharmacological agents. With the repeated endomorphin activity, tolerance develops. Not only will just the treatment of endomorphins increase tolerance, but even the pre-treatment will increase the development of tolerance. Eventually, tolerance leads to addiction. Locomotor activity with the administration of endomorphin-1 and endomorphin-2 were evaluated and corresponded with an increase in the horizontal and vertical activity known as hyperlocomotion. This is still a topic of debate.^[7]

Location

The location of endomorphin activity has been isolated using radioimmunoassay and immunocytochemistry within human, mice, rat, and monkey nervous systems. Both endomorphin tetrapeptides are co-localized in the central nervous system and can both be found in certain areas of the brain. In the midbrain, endomorphin-1 can be found in the hypothalamus, thalamus, and striatum. Within the telencephalon, endomorphin-1 has been identified in the nucleus accumbens and lateral septum. In the hindbrain, more endomorphin-1 reactive neurons have been detected compared to endomorphin-2. Alternately, endomorphin-2, , is predominantly found in the spinal cord. Specifically, endomorphin-2 is found in the dorsal horn region of the spinal cord, especially in the presynaptic terminals of afferent neurons leading to the spinal cord. It has been found co-localized with calcitonin as well as substance P. Neither endomorphin-1 or 2 were found in the amgydala or the hippocampus.^[2]

Clinical application

In addition to endomorphins, morphine and morphine-like opiates target the μ-opioid receptor. Thus, endomorphins pose significant potential as analgesics and morphine substitutes.