Characterization of delta-sleep-inducing peptide-evoked release of Met-enkephalin from brain synaptosomes in rats.
Delta-sleep-inducing peptide (DSIP) stimulates the release of Met-enkephalin (Met-ENK) from superfused slices of the rodent lower brainstem in vitro. In our present study, DSIP (10(-10)-10(-9) M) induced a significant release of Met-ENK from medullary synaptosomes of rats. This DSIP-evoked release of Met-ENK was Ca2+ dependent and tetrodotoxin (TTX) insensitive. Furthermore, DSIP (10(-11)-10(-9) M) significantly increased 45Ca2+ uptake in medullary synaptosomes. These results demonstrate that DSIP acts directly on the nerve endings of Met-ENK-containing neurons to release this pentapeptide by generating a Ca2+ influx into these neurons. Effects of DSIP on Met-ENK release in other discrete brain regions were also studied. Significant DSIP-evoked Met-ENK release from synaptosomes was observed in the cortex, hypothalamus, and midbrain (at concentrations of 10(-10) and 10(-9) M) and in the hippocampus and thalamus (only at 10(-9) M), but not in the striatum. In the hypothalamus, the release of Leu-enkephalin from its synaptosomes was slightly, but not significantly, enhanced by DSIP (10(-10)-10(-8) M). Our findings demonstrate that DSIP triggered a Ca2+ influx in nerve endings to induce a subsequent release of Met-ENK from neurons in only certain brain regions.
Nakamura
A
A
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Sakai
K
K
Takahashi
Y
Y
Shiomi
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D002118:Calcium / Q000493:pharmacokinetics / Q000502:physiology; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D003701:Delta Sleep-Inducing Peptide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000648:ultrastructure; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002132:Calcium Radioisotopes; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D003701:Delta Sleep-Inducing Peptide; D002118:Calcium