2 research outputs found
Anticonvulsant effects of mu (DAGO) and delta (DPDPE) enkephalins in rats
The effects of highly selective mu and delta opioid peptide agonists were determined in two rat models of experimentally-induced convulsions, the flurothyl threshold test and the maximal electroshock test. Intracerebroventricular injections of the mu selective enkephalin DAGO (0.3-2.2 nmol) resulted in a dose-related protection in both seizure models. Pretreatment with a low dose of naloxone (29 nmol) or the irreversible mu antagonist [beta]-FNA (21 nmol), but not the delta opioid antagonist ICI 154,129 (50 nmol), antagonized the anticonvulsant actions of DAGO. Intracerebroventricular injections of the delta selective enkephalin DPDPE (70-140 nmol) also resulted in seizure protection. These effects were selectively antagonized by the delta antagonist ICI 174,864 (2.8 nmol), but not by pretreatment with [beta]-FNA. Thus, using agonists and antagonists highly selective for mu and delta opioid receptors, anticonvulsant actions of enkephalin have been described against chemically- and electrically-induced convulsions in rats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27170/1/0000167.pd
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Hindlimb paralytic effects of prodynorphin-derived peptides following spinal subarachnoid injection in rats
Dynorphin A-(1–17) acts through non-opioid mechanisms to produce dose-related neurological deficits following injection into the lumbar spinal subarachnoid space in rats. Hindlimb motor function was examined following subarachnoid injection of dynorphin A fragments and other opioid peptides derived from prodynorphin to establish: (1) which portion(s) of the dynorphin A molecule cause hindlimb motor dysfunction, and (2) whether these paralytic actions are shared by other opioids (dynorphin B, α-neo-endorphin, and β-neo-endorphin) derived from the same promolecule. To minimize the influence of enzymatic inactivation on relative bioactivities, peptides were coinjected with a combination of peptidase inhibitors previously shown to enhance the actions of dynorphin A fragments in vitro. Dynorphin A-(1–17) and -(2–17) produced dose-related neurological deficits with equal potencies and durations. Although without effect when injected alone, dynorphin A-(1–8), -(1–7) and -(3–8) caused transient motor dysfunction when co-injected with peptidase inhibitors. In contrast, dynorphin A-(1–6), -(1–5) and -(6–17) did not disrupt hindlimb motor function with or without peptidase inhibition. Dynorphin B, α-neo-endorphin also caused hindlimb dysfunction which was potentiated by peptidase inhibition. These deficits appeared to result from non-opioid actions of these three peptides, since they were not blocked by the opioid antagonist naloxone. Thus, the paralytic effects of dynorphin A: (1) result from non-opioid actions involving the 3–7 or 3–8 positions of the molecule, and (2) are shared by other prodynorphin-derived opioid peptides