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Endomorphins: Novel Endogenous μ‐Opiate Receptor Agonists in Regions of High μ‐Opiate Receptor Density
Author(s) -
ZADINA JAMES E.,
MARTINSCHILD SHERYL,
GERALL ARNOLD A.,
KASTIN ABBA J.,
HACKLER LASZLO,
GE LINJUN,
ZHANG XING
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07885.x
Subject(s) - opiate , endogeny , receptor , chemistry , agonist , pharmacology , medicine , endocrinology
A bstract : Endomorphin‐1 (Tyr‐Pro‐Trp‐Phe‐NH 2 , EM‐1) and endomorphin‐2 (Tyr‐Pro‐Phe‐Phe‐NH 2 , EM‐2) are peptides recently isolated from brain that show the highest affinity and selectivity for the m (morphine) opiate receptor of all the known endogenous opioids. The endomorphins have potent analgesic and gastrointestinal effects. At the cellular level, they activate G‐proteins ( 35 S‐GTP γ‐S binding) and inhibit calcium currents. Support for their role as endogenous ligands for the μ‐opiate receptor includes their localization by radioimmunoassay and immunocytochemistry in central nervous system regions of high μ receptor density. Intense EM‐2 immunoreactivity is present in the terminal regions of primary afferent neurons in the dorsal horn of the spinal cord and in the medulla near high densities of μ receptors. Chemical (capsaicin) and surgical (rhizotomy) disruption of nociceptive primary afferent neurons depletes the immunoreactivity, implicating the primary afferents as the source of EM‐2. Thus, EM‐2 is well‐positioned to serve as an endogenous modulator of pain in its earliest stages of perception. In contrast to EM‐2, which is more prevalent in the spinal cord and lower brainstem, EM‐1 is more widely and densely distributed throughout the brain than EM‐2. The distribution is consistent with a role for the peptides in the modulation of diverse functions, including autonomic, neuroendocrine, and reward functions as well as modulation of responses to pain and stress.