Evidence that inhibition of nicotine-mediated catecholamine secretion from adrenal chromaffin cells by enkephalin, beta-endorphin, dynorphin (1-13), and opiates is not mediated via specific opiate receptors.
The opioid peptides Met- and Leu-enkephalin, dynorphin (1-13), and beta-endorphin and the narcotic analgesics, morphine, levorphanol, and dextrorphan all produced a dose-dependent inhibition of nicotine (5 x 10(-6) M)-mediated release of [3H]norepinephrine ([3H]NE) from bovine adrenal chromaffin cells in culture. None of these agents affected [3H]NE release induced by high K+ (56 mM). Although the above results suggest that the opioid peptides and narcotic analgesics inhibit catecholamine release from adrenal chromaffin cells in culture, we suggest that these effects are not mediated by specific opiate binding sites, since (1) the inhibition was only produced with high concentrations of the agents--the threshold concentrations were 10(-7) to 10(-5)M and higher; (2) the inhibition produced by the narcotic analgesics did not display stereospecificity, because the d-isomer, dextrorphan, was slightly more active than the l-isomer, levorphanol; (3) the narcotic antagonists naloxone, naltrexone, and levallorphan did not reverse the inhibition produced by either the narcotic analgesics (e.g., morphine) or the opioid peptides (e.g., dynorphin). These three antagonists themselves inhibited the nicotine-mediated release of [3H]NE from the adrenal chromaffin cells in culture. Finally (4), the I2-Tyr1 substituted analogues of beta-endorphin and dynorphin that are biologically less active than the parent compounds produced an inhibition of the nicotine-mediated [3H]NE release similar to that of their parent compounds. These results do not support the idea that high-affinity stereospecific opiate binding sites are involved in the inhibitory modulation of nicotinic evoked catecholamine release from bovine adrenal chromaffin cells in culture.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002837:Chromaffin Granules / Q000502:physiology*; D002838:Chromaffin System / Q000502:physiology*; D004399:Dynorphins; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000494:pharmacology*; D007700:Kinetics; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D001615:beta-Endorphin
D004723:Endorphins; D004745:Enkephalins; D009294:Narcotics; D010446:Peptide Fragments; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D009538:Nicotine; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; D009638:Norepinephrine