RT Journal Article
SR Electronic
T1 Spinal release of immunoreactive Met-enkephalin by intraventricular beta-endorphin and its analogs in anesthetized rats.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 65
OP 74
VO 237
IS 1
A1 L F Tseng
A1 J F Towell
A1 J M Fujimoto
YR 1986
UL http://jpet.aspetjournals.org/content/237/1/65.abstract
AB We have reported previously that i.v.t. beta-endorphin increases the release of immunoreactive Met-enkephalin but not Leuenkephalin or dynorphins from the spinal cord. To determine if the effect is specific to beta-endorphin, the present investigation tested i.v.t. beta-endorphin, its analogs and other opiate agonists with different opioid receptor activities for their ability to release Met-enkephalin using an intrathecal perfusion technique. Human beta-endorphin and its analogs, human beta-endorphin-(1-30), -(1-29) and -(1-28) which have an identical amino acid sequence in the NH2-terminus showed reduced stepwise potencies in releasing Met-enkephalin. The results correlated well with their analgesic potencies. Des-Met5-camel beta-endorphin (64 micrograms i.v.t.) which does not have a complete sequence of Met-enkephalin in its NH2-terminus but still retains 20% of camel beta-endorphin analgesic potency caused the spinal release of Met-enkephalin. Morphine (mu opioid receptor agonist, 40 micrograms), D-Ala2-D-Leu5-enkephalin (delta opioid receptor agonist, 80 micrograms) and U-50488H (kappa opioid receptor agonist, 160 micrograms) injected i.v.t. were unable to cause any release of Met-enkephalin. High-performance liquid chromatography after Sephadex G-50 gel chromatography indicated that the immunoreactive Met-enkephalin in the spinal perfusate released by i.v.t. beta-endorphin had a retention time identical to authentic Met-enkephalin. Intraventricular injection of Met-enkephalin, 4 nmol (2.3 micrograms), caused little increase of Met-enkephalin immunoreactivity in the spinal perfusate, whereas 4 nmol of i.v.t. beta-endorphin caused a marked increase of Met-enkephalin in the spinal perfusate. Inhibition of peptidase by i.v.t. aprotinin and bacitracin does not prevent the spinal release of Met-enkephalin induced by i.v.t. beta-endorphin. It is concluded that the release of Met-enkephalin was specific to beta-endorphin and the results were not due to cross-immunoreactivity of beta-endorphin or its metabolites.