Effects of opioid peptides containing the sequence of Met5-enkephalin or Leu5-enkephalin on nicotine-induced secretion from bovine adrenal chromaffin cells.
Eighteen endogenous opioid peptides, all containing the sequence of either Met5- or Leu5-enkephalin, were tested for their ability to modify nicotine-induced secretion from bovine adrenal chromaffin cells. ATP released from suspensions of freshly isolated cells was measured with the luciferin-luciferase bioluminescence method as an index of secretion. None of the peptides affected 5 microM nicotine-induced ATP release at 10 nM. Three peptides inhibited secretion at 5 microM: dynorphin1-13, dynorphin1-9, and rimorphin inhibited by 65%, 37%, and 29% respectively. Use of peptidase inhibitors (bestatin, thiorphan, bacitracin, or 1,10-phenanthroline) did not result in any of the other peptides showing potent actions on the nicotinic response, although bestatin and thiorphan did enhance the inhibitory actions of dynorphin1-13 and dynorphin1-9 by 20-30%. Nicotine-induced secretion of endogenous catecholamines from bovine chromaffin cells cultured for 3 days was also studied to assess any selective actions of the peptides on adrenaline or noradrenaline cell types. Dynorphin1-13 was 1,000-fold more potent than Leu5-enkephalin at inhibiting endogenous catecholamine secretion. Dynorphin1-13 was slightly more potent at inhibiting noradrenaline release than adrenaline release whereas Leu5-enkephalin showed the opposite selectivity. The structure-activity relationships of opioid peptide actions on the chromaffin cell nicotinic response are discussed in relation to the properties of the adrenal opioid binding sites.
Marley
P D
PD
Mitchelhill
K I
KI
Livett
B G
BG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D002417:Cattle; D004399:Dynorphins / Q000494:pharmacology; D004723:Endorphins / Q000235:genetics / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000235:genetics / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000235:genetics / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D006168:Guinea Pigs; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology
D004723:Endorphins; D010446:Peptide Fragments; D010618:Phenanthrolines; D011957:Receptors, Opioid; D001414:Bacitracin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009538:Nicotine; C026843:dynorphin (1-13); D004399:Dynorphins; D000255:Adenosine Triphosphate; D015244:Thiorphan; D008625:Tiopronin; D007930:Leucine; C012211:ubenimex; C025205:1,10-phenanthroline; D009638:Norepinephrine; D004837:Epinephrine